Journal articles on the topic 'Kidney epithelial cells'
To see the other types of publications on this topic, follow the link: Kidney epithelial cells.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Kidney epithelial cells.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Pastor-Soler, Núria M., Timothy A. Sutton, Henry E. Mang, Carol L. Kinlough, Sandra J. Gendler, Cathy S. Madsen, Sheldon I. Bastacky, et al. "Muc1 is protective during kidney ischemia-reperfusion injury." American Journal of Physiology-Renal Physiology 308, no. 12 (June 15, 2015): F1452—F1462. http://dx.doi.org/10.1152/ajprenal.00066.2015.
Abstract:
Ischemia-reperfusion injury (IRI) due to hypotension is a common cause of human acute kidney injury (AKI). Hypoxia-inducible transcription factors (HIFs) orchestrate a protective response in renal endothelial and epithelial cells in AKI models. As human mucin 1 (MUC1) is induced by hypoxia and enhances HIF-1 activity in cultured epithelial cells, we asked whether mouse mucin 1 (Muc1) regulates HIF-1 activity in kidney tissue during IRI. Whereas Muc1 was localized on the apical surface of the thick ascending limb, distal convoluted tubule, and collecting duct in the kidneys of sham-treated mice, Muc1 appeared in the cytoplasm and nucleus of all tubular epithelia during IRI. Muc1 was induced during IRI, and Muc1 transcripts and protein were also present in recovering proximal tubule cells. Kidney damage was worse and recovery was blocked during IRI in Muc1 knockout mice compared with congenic control mice. Muc1 knockout mice had reduced levels of HIF-1α, reduced or aberrant induction of HIF-1 target genes involved in the shift of glucose metabolism to glycolysis, and prolonged activation of AMP-activated protein kinase, indicating metabolic stress. Muc1 clearly plays a significant role in enhancing the HIF protective pathway during ischemic insult and recovery in kidney epithelia, providing a new target for developing therapies to treat AKI. Moreover, our data support a role specifically for HIF-1 in epithelial protection of the kidney during IRI as Muc1 is present only in tubule epithelial cells.
2
Verghese, George M., Michael F. Gutknecht, and George H. Caughey. "Prostasin regulates epithelial monolayer function: cell-specific Gpld1-mediated secretion and functional role for GPI anchor." American Journal of Physiology-Cell Physiology 291, no. 6 (December 2006): C1258—C1270. http://dx.doi.org/10.1152/ajpcell.00637.2005.
Abstract:
Prostasin, a trypsinlike serine peptidase, is highly expressed in prostate, kidney, and lung epithelia, where it is bound to the cell surface, secreted, or both. Prostasin activates the epithelial sodium channel (ENaC) and suppresses invasion of prostate and breast cancer cells. The studies reported here establish mechanisms of membrane anchoring and secretion in kidney and lung epithelial cells and demonstrate a critical role for prostasin in regulating epithelial monolayer function. We report that endogenous mouse prostasin is glycosylphosphatidylinositol (GPI) anchored to the cell surface and is constitutively secreted from the apical surface of kidney cortical collecting duct cells. Using site-directed mutagenesis, detergent phase separation, and RNA interference approaches, we show that prostasin secretion depends on GPI anchor cleavage by endogenous GPI-specific phospholipase D1 (Gpld1). Secretion of prostasin by kidney and lung epithelial cells, in contrast to prostate epithelium, does not depend on COOH-terminal processing at conserved Arg322. Using stably transfected M-1 cells expressing wild-type, catalytically inactive, or chimeric transmembrane (not GPI)-anchored prostasins we establish that prostasin regulates transepithelial resistance, current, and paracellular permeability by GPI anchor- and protease activity-dependent mechanisms. These studies demonstrate a novel role for prostasin in regulating epithelial monolayer resistance and permeability in kidney epithelial cells and, furthermore, show specifically that prostasin is a critical regulator of transepithelial ion transport in M-1 cells. These functions depend on the GPI anchor as well as the peptidase activity of prostasin. These studies suggest that cell-specific Gpld1- or peptidase-dependent pathways for prostasin secretion may control prostasin functions in a tissue-specific manner.
3
Kim, Bo Hye, Do Yeon Kim, Yejin Ahn, Eun Ji Lee, Hyunjoo Park, Meeyoung Park, and Jong Hoon Park. "Semaphorin-3C Is Upregulated in Polycystic Kidney Epithelial Cells and Inhibits Angiogenesis of Glomerular Endothelial Cells." American Journal of Nephrology 51, no. 7 (2020): 556–64. http://dx.doi.org/10.1159/000508263.
Abstract:
Background: Polycystic kidney disease (PKD) is a hereditary disease characterized by cyst formation in the kidneys bilaterally. It has been observed that semaphorin-3C (SEMA3C) is overexpressed in polycystic kidney epithelial cells. It is hypothesized that upregulated SEMA3C would contribute to survival of polycystic kidney epithelial cells. Furthermore, as the kidney is a highly vascularized organ, the secreted SEMA3C from PKD epithelial cells will affect glomerular endothelial cells (GECs) in a paracrine manner. Methods: To evaluate the effect of SEMA3C on renal cells, siSEMA3C-treated PKD epithelial cells were used for further analysis, and GECs were exposed to recombinant SEMA3C (rSEMA3C). Also, co-culture and treatment of conditioned media were employed to confirm whether PKD epithelial cells could influence on GECs via SEMA3C secretion. Results: SEMA3C knockdown reduced proliferation of PKD epithelial cells. In case of GECs, exposure to rSEMA3C decreased angiogenesis, which resulted from suppressed migratory ability not cell proliferation. Conclusions: This study indicates that SEMA3C is the aggravating factor in PKD. Thus, it is proposed that targeting SEMA3C can be effective to mitigate PKD.
4
TUFRO, ALDA, VICTORIA F. NORWOOD, ROBERT M. CAREY, and R. ARIEL GOMEZ. "Vascular Endothelial Growth Factor Induces Nephrogenesis and Vasculogenesis." Journal of the American Society of Nephrology 10, no. 10 (October 1999): 2125–34. http://dx.doi.org/10.1681/asn.v10102125.
Abstract:
Abstract. The expression of vascular endothelial growth factor (VEGF) and its receptors Flt-1 and Flk-1 in the rat kidney was examined during ontogeny using Northern blot analysis and immunocytochemistry. In prevascular embryonic kidneys (embryonic day 14 [E14]), immunoreactive Flt-1 and Flk-1 were observed in isolated angioblasts, whereas VEGF was not detected. Angioblasts aligned forming cords before morphologically differentiating into endothelial cells. In late fetal kidneys (E19), immunoreactive VEGF was detected in glomerular epithelial and tubular cells, whereas Flt-1 and Flk-1 were expressed in contiguous endothelial cells. To determine whether VEGF induces endothelial cell differentiation and vascular development in the kidney, the effect of recombinant human VEGF (5 ng/ml) was examined on rat metanephric organ culture, a model known to recapitulate nephrogenesis in the absence of vessels. After 6 d in culture in serum-free, defined media, metanephric kidney growth and morphology were assessed. DNA content was higher in VEGF-treated explants (1.9 ± 0.17 μg/kidney, n = 9) than in paired control explants (1.4 ± 0.10 μg/kidney, n = 9) (P < 0.05). VEGF induced proliferation of tubular epithelial cells, as indicated by an increased number of tubules and tubular proliferating cell nuclear antigen-containing cells. VEGF induced upregulation of Flk-1 and Flt-1 expression, as assessed by Western blot analysis. Developing endothelial cells were identified and localized using immunocytochemistry and electron microscopy. Flt-1, Flk-1, and angiotensin-converting enzyme-containing cells were detected in VEGF-treated explants, whereas control explants were negative. These studies confirmed previous reports indicating that the expression of VEGF and its receptors is temporally and spatially associated with kidney vascularization and identified angioblasts expressing Flt-1 and Flk-1 in prevascular embryonic kidneys. The data indicate that VEGF expression is downregulated in standard culture conditions and that VEGF stimulates growth of embryonic kidney explants by expanding both endothelium and epithelium, resulting in vasculogenesis and enhanced tubulogenesis. These data suggest that VEGF plays a critical role in renal development by promoting endothelial cell differentiation, capillary formation, and proliferation of tubular epithelia.
5
Cramer, E. B., L. C. Milks, M. J. Brontoli, G. K. Ojakian, S. D. Wright, and H. J. Showell. "Effect of human serum and some of its components on neutrophil adherence and migration across an epithelium." Journal of Cell Biology 102, no. 5 (May 1, 1986): 1868–77. http://dx.doi.org/10.1083/jcb.102.5.1868.
Abstract:
The effect of human serum and some of its components on the process of transepithelial migration of human neutrophils was investigated in an in vitro system. 10% autologous serum caused an increase in neutrophil adherence to and migration across canine kidney epithelial cells. This increase in neutrophil binding also occurred if the epithelium but not the neutrophils had been preincubated with serum. The binding was lost if the serum was either preabsorbed over the kidney epithelium before use or heat inactivated. Indirect immunofluorescence studies indicated that IgG, IgM, and a component of C3 bound to the epithelial surface, whereas IgA, IgE, or C5a were not detectable. The majority of epithelial cells were immunofluorescent, however epithelial cells with varying degrees of reactivity were also apparent and approximately 5% of the epithelial cells did not bind IgG, IgM, and C3. When epithelia were simultaneously tested for the presence of either IgG, IgM, or C3, and bound neutrophils the few epithelial cells which did not bind IgG or IgM also did not bind C3 or neutrophils. Studies with monoclonal antibodies against Fc and C3 receptors indicate that neutrophil adherence to the epithelial surface was mediated predominately by the receptors for C3b and C3bi. In response to a chemotactic gradient, bound neutrophils were able to detach and migrate across the epithelium. A separate heat-stable factor(s) in serum was able to increase neutrophil migration across the epithelial monolayer. This factor acted independently of the factors which caused the increase in neutrophil binding as the increase in neutrophil migration also occurred under conditions (preabsorption over the kidney epithelium or heat inactivation) that prevented the increase in neutrophil binding. The increase in neutrophil migration may be caused by the permeability-increasing properties of this factor as both serum and heat-inactivated serum lowered the transepithelial electrical resistance an average of 38 and 35%, respectively, in 40 min. Upon removal of serum or heat-inactivated serum, the resistance returned 100 and 81%, respectively, in 5 h.
6
Kuberka, M., G. Rau, and B. Glasmacher. "CRYOPRESERVATION OF EPITHELIAL KIDNEY CELLS." Biomedizinische Technik/Biomedical Engineering 48, s1 (2003): 322–23. http://dx.doi.org/10.1515/bmte.2003.48.s1.322.
7
Dahl, Ulf, Anders Sjödin, Lionel Larue, Glenn L. Radice, Stefan Cajander, Masatoshi Takeichi, Rolf Kemler, and Henrik Semb. "Genetic Dissection of Cadherin Function during Nephrogenesis." Molecular and Cellular Biology 22, no. 5 (March 1, 2002): 1474–87. http://dx.doi.org/10.1128/mcb.22.5.1474-1487.2002.
Abstract:
ABSTRACT The distinct expression of R-cadherin in the induced aggregating metanephric mesenchyme suggests that it may regulate the mesenchymal-epithelial transition during kidney development. To address whether R-cadherin is required for kidney ontogeny, R-cadherin-deficient mice were generated. These mice appeared to be healthy and were fertile, demonstrating that R-cadherin is not essential for embryogenesis. The only kidney phenotype of adult mutant animals was the appearance of dilated proximal tubules, which was associated with an accumulation of large intracellular vacuoles. Morphological analysis of nephrogenesis in R-cadherin −/− mice in vivo and in vitro revealed defects in the development of both ureteric bud-derived cells and metanephric mesenchyme-derived cells. First, the morphology and organization of the proximal parts of the ureteric bud epithelium were altered. Interestingly, these morphological changes correlated with an increased rate of apoptosis and were further supported by perturbed branching and patterning of the ureteric bud epithelium during in vitro differentiation. Second, during in vitro studies of mesenchymal-epithelial conversion, significantly fewer epithelial structures developed from R-cadherin −/− kidneys than from wild-type kidneys. These data suggest that R-cadherin is functionally involved in the differentiation of both mesenchymal and epithelial components during metanephric kidney development. Finally, to investigate whether the redundant expression of other classic cadherins expressed in the kidney could explain the rather mild kidney defects in R-cadherin-deficient mice, we intercrossed R-cadherin −/− mice with cadherin-6−/− , P-cadherin −/−, and N-cadherin +/− mice. Surprisingly, however, in none of the compound knockout strains was kidney development affected to a greater extent than within the individual cadherin knockout strains.
8
Pat, Betty, David W. Johnson, and Glenda C. Gobe. "Role of JAK3 in the Pathogenesis of Oxidative Stress-Induced Kidney Fibrosis." Journal of Renal and Hepatic Disorders 2, no. 1 (May 14, 2018): 18–26. http://dx.doi.org/10.15586/jrenhep.2018.30.
Abstract:
The Janus kinase (JAK) tyrosine kinase family and JAK/STAT signal transduction pathway may act in kidney fibrogenesis. JAK3 expression was investigated in in vitro and in vivo models of kidney fibrosis involving oxidative stress. There was a marked down-regulation of JAK3 mRNA in rat kidney tubular epithelial cells (NRK52E) and fibroblasts (NRK49F) exposed to 1.0 mM H2O2 for 18–20 h compared with controls, which correlated with increased apoptosis and decreased mitosis in both cell lines. However, JAK3 protein levels were not significantly different in control and H2O2-treated epithelial and fibroblast cultures. JAK3 activation (phospho-tyrosine) increased in NRK52E cells and decreased in NRK49F cells with oxidative stress. STAT3 phosphorylation decreased in both cell lines with oxidative stress compared with controls. JAK3 protein expression and localisation were investigated in kidneys using the unilateral ureteral obstruction (UUO) model (0–7 days, rats) of kidney fibrosis that involves oxidative stress. JAK3 protein expression did not differ between UUO and controls; however, JAK3 localisation increased temporally with UUO, with strong epithelial expression in mitotic cells compared with controls. Apoptotic tubular epithelium showed minimal JAK3. In summary, in vitro, decreased kidney JAK3 mRNA after oxidative stress was not seen translationally. Differences in the activation of the JAK3/STAT3 pathway may have different consequences for renal fibrosis. In vivo, changes in JAK3 protein localisation, and especially its co-localisation with mitotic cells, indicate that JAK3 protein may contribute to renal tubular epithelial cell proliferation after oxidative stress.
9
White, Lindsay R., Jason B. Blanchette, Li Ren, Ali Awn, Kiril Trpkov, and Daniel A. Muruve. "The characterization of α5-integrin expression on tubular epithelium during renal injury." American Journal of Physiology-Renal Physiology 292, no. 2 (February 2007): F567—F576. http://dx.doi.org/10.1152/ajprenal.00212.2006.
Abstract:
The hallmark of progressive chronic kidney disease is the deposition of extracellular matrix proteins and tubulointerstitial fibrosis. Integrins mediate cell-extracellular matrix interaction and may play a role tubular epithelial injury. Murine primary tubular epithelial cells (TECs) express α5-integrin, a fibroblast marker and the natural receptor for fibronectin. Microscopy localized α5-integrin on E-cadherin-positive cells, confirming epithelial expression. The expression of α5-integrin increased in TECs grown on fibronectin and occurred in parallel with an upregulation of α-smooth muscle actin (αSMA), a marker of epithelial-mesenchymal transition (EMT). Exposure of TECs to transforming growth factor (TGF)-β also increased TEC α5-integrin expression in association with αSMA and EMT. Knock-down of α5-integrin expression with short interfering RNA attenuated the TGF-β induction of αSMA but did not alter morphologic EMT. Rather, α5-integrin was necessary for epithelial cell migration on fibronectin but not type IV collagen during cell spreading and epithelial wound healing in vitro. Immunohistochemistry revealed basolateral tubular epithelial α5-integrin expression in mouse kidneys after unilateral ureteric obstruction but not in contralateral control kidneys. In patient biopsies of nondiabetic kidney disease, α5-integrin expression was increased significantly in the renal interstitium. Focal basolateral staining was also detected in injured, but not in normal, tubular epithelium. In summary, these data show that TECs are induced to express α5-integrin during EMT and tubular epithelial injury in vitro and in vivo. These results increase our understanding of the biology of integrins during EMT and tubular injury in chronic kidney disease.
10
Sorokin, L., A. Sonnenberg, M. Aumailley, R. Timpl, and P. Ekblom. "Recognition of the laminin E8 cell-binding site by an integrin possessing the alpha 6 subunit is essential for epithelial polarization in developing kidney tubules." Journal of Cell Biology 111, no. 3 (September 1, 1990): 1265–73. http://dx.doi.org/10.1083/jcb.111.3.1265.
Abstract:
It has been previously shown that A-chain and domain(E8)-specific antibodies to laminin that inhibit cell adhesion also interfere with the establishment of epithelial cell polarity during kidney tubule development (Klein, G., M. Langegger, R. Timpl, and P. Ekblom. 1988. Cell. 55:331-341). A monoclonal antibody specific for the integrin alpha 6 subunit, which selectively blocks cell binding to E8, was used to study the receptors involved. Immunofluorescence staining of embryonic kidneys and of organ cultures of metanephric mesenchyme demonstrated coappearance of the integrin alpha 6 subunit and the laminin A-chain in regions where nonpolarized mesenchymal cells convert into polarized epithelial cells. Both epitopes showed marked colocalization in basal areas of tubules, while an exclusive immunostaining for alpha 6 was observed in lateral and apical cell surfaces of the tubular epithelial cells. Organ culture studies demonstrated a consistent inhibition of kidney epithelium development by antibodies against the alpha 6 subunit. The data suggest that the recognition of E8 cell-binding site of laminin by a specific integrin is crucial for the formation of kidney tubule epithelium from undifferentiated mesenchymal stem cells. In some other cell types (endothelium, some ureter cells) an exclusive expression of alpha 6 with no apparent colocalization of laminin A-chain in the corresponding basement membrane was seen. Thus, in these cells, integrins possessing the alpha 6 subunit may bind to laminin isoforms that differ from those synthesized by developing tubules.
11
Iida, Manami, Shuichi Ohtomo, Naoko A. Wada, Otoya Ueda, Yoshinori Tsuboi, Atsuo Kurata, Kou-ichi Jishage, and Naoshi Horiba. "TNF-α induces Claudin-1 expression in renal tubules in Alport mice." PLOS ONE 17, no. 3 (March 10, 2022): e0265081. http://dx.doi.org/10.1371/journal.pone.0265081.
Abstract:
Claudin-1 (CL-1) is responsible for the paracellular barrier function of glomerular parietal epithelial cells (PEC) in kidneys, but the role of CL-1 in proximal tubules remains to be elucidated. In this study, to evaluate CL-1 as a potential therapeutic drug target for chronic kidney disease, we investigated change of CL-1 expression in the proximal tubules of diseased kidney and elucidated the factors that induced this change. We established Alport mice as a kidney disease model and investigated the expression of CL-1 in diseased kidney using quantitative PCR and immunohistochemistry (IHC). Compared to wild type mice, Alport mice showed significant increases in plasma creatinine, urea nitrogen and urinary albumin excretion. CL-1 mRNA was increased significantly in the kidney cortex and CL-1 was localized on the adjacent cell surfaces of PECs and proximal tubular epithelial cells. The infiltration of inflammatory cells around proximal tubules and a significant increase in TNF-α mRNA were observed in diseased kidneys. To reveal factors that induce CL-1, we analyzed the induction of CL-1 by albumin or tumor necrosis factor (TNF)-α in human proximal tubular cells (RPTEC/TERT1) using quantitative PCR and Western blotting. TNF-α increased CL-1 expression dose-dependently, though albumin did not affect CL-1 expression in RPTEC/TERT1. In addition, both CL-1 and TNF-α expression were significantly increased in UUO mice, which are commonly used as a model of tubulointerstitial inflammation without albuminuria. These results indicate that CL-1 expression is induced by inflammation, not by albuminuria in diseased proximal tubules. Moreover, we examined the localization of CL-1 in the kidney of IgA nephropathy patients by IHC and found CL-1 expression was also elevated in the proximal tubular cells. Taken together, CL-1 expression is increased in the proximal tubular epithelial cells of diseased kidney. Inflammatory cells around the tubular epithelium may produce TNF-α which in turn induces CL-1 expression.
12
Mukherjee, Malini, Jennifer deRiso, Karla Otterpohl, Ishara Ratnayake, Divya Kota, Phil Ahrenkiel, Indra Chandrasekar, and Kameswaran Surendran. "Endogenous Notch Signaling in Adult Kidneys Maintains Segment-Specific Epithelial Cell Types of the Distal Tubules and Collecting Ducts to Ensure Water Homeostasis." Journal of the American Society of Nephrology 30, no. 1 (December 4, 2018): 110–26. http://dx.doi.org/10.1681/asn.2018040440.
Abstract:
BackgroundNotch signaling is required during kidney development for nephron formation and principal cell fate selection within the collecting ducts. Whether Notch signaling is required in the adult kidney to maintain epithelial diversity, or whether its loss can trigger principal cell transdifferentiation (which could explain acquired diabetes insipidus in patients receiving lithium) is unclear.MethodsTo investigate whether loss of Notch signaling can trigger principal cells to lose their identity, we genetically inactivated Notch1 and Notch2, inactivated the Notch signaling target Hes1, or induced expression of a Notch signaling inhibitor in all of the nephron segments and collecting ducts in mice after kidney development. We examined renal function and cell type composition of control littermates and mice with conditional Notch signaling inactivation in adult renal epithelia. In addition, we traced the fate of genetically labeled adult kidney collecting duct principal cells after Hes1 inactivation or lithium treatment.ResultsNotch signaling was required for maintenance of Aqp2-expressing cells in distal nephron and collecting duct segments in adult kidneys. Fate tracing revealed mature principal cells in the inner stripe of the outer medulla converted to intercalated cells after genetic inactivation of Hes1 and, to a lesser extent, lithium treatment. Hes1 ensured repression of Foxi1 to prevent the intercalated cell program from turning on in mature Aqp2+ cell types.ConclusionsNotch signaling viaHes1 regulates maintenance of mature renal epithelial cell states. Loss of Notch signaling or use of lithium can trigger transdifferentiation of mature principal cells to intercalated cells in adult kidneys.
13
LORZ, CORINA, ALBERTO ORTIZ, PILAR JUSTO, SILVIA GONZÁLEZ-CUADRADO, NATALIA DUQUE, CARMEN GÓMEZ-GUERRERO, and JESÚS EGIDO. "Proapoptotic Fas Ligand Is Expressed by Normal Kidney Tubular Epithelium and Injured Glomeruli." Journal of the American Society of Nephrology 11, no. 7 (July 2000): 1266–77. http://dx.doi.org/10.1681/asn.v1171266.
Abstract:
Abstract. Fas ligand (FasL) is a cell membrane cytokine that can promote apoptosis through activation of Fas receptors. Fas receptor activation induces glomerular cell apoptosisin vivoand participates in tubular cell death during acute renal failure. However, there is little information on the expression of FasL in the kidney. This study reports that FasL mRNA and protein are present in normal mouse and rat kidney.In situhybridization and immunohistochemistry showed that proximal tubular epithelium is the main site of FasL expression in the normal kidney. In addition, increased total kidney FasL mRNA andde novoFasL protein expression by glomerular cells were observed in two different models of glomerular injury : rat immune-complex proliferative glumerulonephritis and murine lupus nephritis. Both full-length and soluble FasL were increased in the kidneys of the mice with nephritis. Cultured murine proximal tubular epithelial MCT cells and primary cultures of murine tubular epithelial cells expressed FasL mRNA and protein. Tubular epithelium-derived FasL induced apoptosis in Fassensitive lymphoid cell lines but not in Fas-resistant lymphoid cell lines. By contrast, MCT cells grown in the presence of the survival factors of serum were resistant to FasL, and only became partially sensitive to apoptosis induced by high concentrations (100 ng/ml) of FasL upon serum deprivation. However, MCT cells stimulated with inflammatory mediators (tumor necrosis factor-α, interferon-γ, and lipopolysaccharide) increased cell surface Fas expression and were sensitized to apoptosis induced by FasL (FasL 55 ± 5%versuscontrol 8.3 ± 4.1% apoptotic cells at 24 h,P< 0.05). Cytokine-primed primary cultures of tubular epithelial cells also acquired sensitivity to FasL-induced apoptosis. These results suggest that FasL expression by intrinsic renal cells may play a role in cell homeostasis in the normal kidney and during renal injury.
14
Stewart, Benjamin J., John R. Ferdinand, Matthew D. Young, Thomas J. Mitchell, Kevin W. Loudon, Alexandra M. Riding, Nathan Richoz, et al. "Spatiotemporal immune zonation of the human kidney." Science 365, no. 6460 (September 26, 2019): 1461–66. http://dx.doi.org/10.1126/science.aat5031.
Abstract:
Tissue-resident immune cells are important for organ homeostasis and defense. The epithelium may contribute to these functions directly or by cross-talk with immune cells. We used single-cell RNA sequencing to resolve the spatiotemporal immune topology of the human kidney. We reveal anatomically defined expression patterns of immune genes within the epithelial compartment, with antimicrobial peptide transcripts evident in pelvic epithelium in the mature, but not fetal, kidney. A network of tissue-resident myeloid and lymphoid immune cells was evident in both fetal and mature kidney, with postnatal acquisition of transcriptional programs that promote infection-defense capabilities. Epithelial-immune cross-talk orchestrated localization of antibacterial macrophages and neutrophils to the regions of the kidney most susceptible to infection. Overall, our study provides a global overview of how the immune landscape of the human kidney is zonated to counter the dominant immunological challenge.
15
Bjerregaard, Henning F. "Electrophysiological Measurements of a Toad Renal Epithelial Cell Line (A6) as an Assay for Predicting Ocular Eye Irritancy." Alternatives to Laboratory Animals 20, no. 2 (April 1992): 218–21. http://dx.doi.org/10.1177/026119299202000206.
Abstract:
An established epithelial cell line (A6) from a South African clawed toad (Xenopus laevis) kidney was used as a model for the corneal epithelium of the eye in order to determine ocular irritancy. When grown on Millipore filter inserts, A6 cells form a monolayer epithelium of high electrical resistance and generate a trans-epithelial potential difference. These two easily-measured electrophysiological endpoints showed a dose-related decrease after exposure for 24 hours to seven selected chemicals of different ocular irritancy potential. It was demonstrated that both trans-epithelial resistance and potential ranked closely with in vivo eye irritancy data and correlated well (r = 0.96) with loss of trans-epithelial impermeability of Madin-Darby canine kidney (MDCK) cells, detected by use of a fluorescein leakage assay.
16
Breuss, J. M., J. Gallo, H. M. DeLisser, I. V. Klimanskaya, H. G. Folkesson, J. F. Pittet, S. L. Nishimura, K. Aldape, D. V. Landers, and W. Carpenter. "Expression of the beta 6 integrin subunit in development, neoplasia and tissue repair suggests a role in epithelial remodeling." Journal of Cell Science 108, no. 6 (June 1, 1995): 2241–51. http://dx.doi.org/10.1242/jcs.108.6.2241.
Abstract:
The alpha v beta 6 integrin was identified in cultured epithelial cells and functions as a fibronectin receptor. We have now used monoclonal antibodies to determine in vivo expression patterns of the beta 6 subunit in normal and pathological human or primate tissues, and during experimental wound healing or induced lung injury. The results indicate that beta 6 expression is restricted to epithelia and is up-regulated in parallel with morphogenetic events, tumorigenesis, and epithelial repair. During development of the kidney, lung, and skin, we found that beta 6 is expressed by specific types of epithelial cells, whereas it is mostly undetectable in normal adult kidney, lung and skin. In contrast, we detected high-level expression in several types of carcinoma. For example, beta 6 is almost invariably neo-expressed in squamous cell carcinomas derived from the oral mucosa, often focally localized at the infiltrating edges of tumor islands. Expression of beta 6 is also upregulated in migrating keratinocytes at the wound edge during experimental epidermal wound healing. Similarly, beta 6 expression is induced in type II alveolar epithelial cells during lung injury caused by injection of live bacteria. We also observed beta 6 expression in adult lungs and kidneys at focal sites of subclinical inflammation, as well as in a variety of clinical specimens from patients with chronic or acute inflammation of the lungs or kidneys. From these findings and earlier results, we hypothesize that alpha v beta 6 affects cell spreading, migration and growth during reorganization of epithelia in development, tissue repair, and neoplasia.
17
Uchida, Takahiro, Hiroyuki Nakashima, Seigo Ito, Takuya Ishikiriyama, Masahiro Nakashima, Shuhji Seki, Hiroo Kumagai, and Naoki Oshima. "Activated natural killer T cells in mice induce acute kidney injury with hematuria through possibly common mechanisms shared by human CD56+ T cells." American Journal of Physiology-Renal Physiology 315, no. 3 (September 1, 2018): F618—F627. http://dx.doi.org/10.1152/ajprenal.00160.2018.
Abstract:
Although activation of mouse natural killer T (NKT) cells by α-galactosylceramide (α-GalCer) causes failure of multiple organs, including the kidneys, the precise mechanisms underlying kidney injury remain unclear. Here, we showed that α-GalCer-activated mouse NKT cells injured both kidney vascular endothelial cells and tubular epithelial cells in vitro, causing acute kidney injury (AKI) with hematuria in middle-aged mice. The perforin-mediated pathway was mainly involved in glomerular endothelial cell injury, whereas the TNF-α/Fas ligand pathway played an important role in the injury of tubular epithelial cells. Kidney injury in young mice was mild but could be significantly exacerbated if NKT cells were strongly activated by NK cell depletion alone or in combination with IL-12 pretreatment. When stimulated by a combination of IL-2 and IL-12, human CD56+ T cells, a functional counterpart of mouse NKT cells, also damaged both glomerular endothelial cells and tubular epithelial cells, with the former being affected in a perforin-dependent manner. These data suggest that both mouse NKT cells and human CD56+ T cells are integral to the processes that mediate AKI. Targeting CD56+ T cells may, therefore, be a promising approach to treat AKI.
18
Loh, N. Y., S. E. Newey, K. E. Davies, and D. J. Blake. "Assembly of multiple dystrobrevin-containing complexes in the kidney." Journal of Cell Science 113, no. 15 (August 1, 2000): 2715–24. http://dx.doi.org/10.1242/jcs.113.15.2715.
Abstract:
Dystrophin is the key component in the assembly and maintenance of the dystrophin-associated protein complex (DPC) in skeletal muscle. In kidney, dystroglycan, an integral component of the DPC, is involved in kidney epithelial morphogenesis, suggesting that the DPC is important in linking the extracellular matrix to the internal cytoskeleton of kidney epithelia. Here, we have investigated the molecular architecture of dystrophin-like protein complexes in kidneys from normal and dystrophin-deficient mice. Using isoform-specific antibodies, we show that the different cell types that make up the kidney maintain different dystrophin-like complexes. These complexes can be broadly grouped according to their dystrobrevin content: beta-dystrobrevin containing complexes are present at the basal region of renal epithelial cells, whilst alpha-dystrobrevin-1 containing complexes are found in endothelial and smooth muscle cells. Furthermore, these complexes are maintained even in the absence of all dystrophin isoforms. Thus our data suggest that the functions and assembly of the dystrophin-like complexes in kidney differ from those in skeletal muscle and implicate a protein other than dystrophin as the primary molecule in the assembly and maintenance of kidney complexes. Our findings also provide a possible explanation for the lack of kidney pathology in Duchenne muscular dystrophy patients and mice lacking all dystrophin isoforms.
19
Wilson, P. D. "Epithelial cell polarity and disease." American Journal of Physiology-Renal Physiology 272, no. 4 (April 1, 1997): F434—F442. http://dx.doi.org/10.1152/ajprenal.1997.272.4.f434.
Abstract:
The establishment and maintenance of epithelial polarity is essential for the integrity and function of epithelial organs and is particularly critical in the kidney, where vectorial reabsorption and secretion are effected in different segments of the nephron by the differential polarized insertion of channels, transporters, and related proteins into apical membranes lining the tubule lumen or basolateral membranes adjacent to the interstitium and blood space. Faulty intracellular delivery and polarization of membrane proteins can lead to serious diseases such as cystic fibrosis, I cell disease, and renal cystic diseases. The best understood disease of epithelial polarity is autosomal dominant polycystic kidney disease (ADPKD) caused by mutations in a >462-kDa, developmentally regulated membrane protein, “polycystin.” ADPKD cysts are characteristically lined by a single layer of structurally polarized epithelial cells with normal functional intercellular tight junctions but with aberrant polarization of some important membrane proteins. Abnormal apical membrane polarity of biochemically active, ouabain-sensitive Na-K-adenosinetriphosphatase (Na-K-ATPase) in ADPKD cyst epithelia leads to abnormal sodium ion secretion and provides a mechanism for aberrant fluid secretion. In addition, apically mislocated, functional epidermal growth factor (EGF) receptors on cyst epithelia, together with EGF synthesis and secretion into cyst lumens, provide a mechanism for autocrine regulation of increased epithelial cell proliferation in ADPKD. Underlying mechanisms for these abnormalities in polarized distribution of membrane proteins include the aberrant expression of fetal gene products, such as the beta2-subunit of Na-K-ATPase, in ADPKD kidneys. Overexpression of polycystin protein in ADPKD cyst epithelia, low levels restricted to medullary collecting tubules in normal adult kidneys, and high levels in ureteric bud-derived structures in human fetal kidneys further suggest a failure of downregulation of fetal genes as a mechanism for the polarity abnormalities that characterize ADPKD.
20
Frigeri, A., M. A. Gropper, F. Umenishi, M. Kawashima, D. Brown, and A. S. Verkman. "Localization of MIWC and GLIP water channel homologs in neuromuscular, epithelial and glandular tissues." Journal of Cell Science 108, no. 9 (September 1, 1995): 2993–3002. http://dx.doi.org/10.1242/jcs.108.9.2993.
Abstract:
It was shown recently that water channel homologs MIWC (mercurial insensitive water channel) and GLIP (glycerol intrinsic protein) colocalized in basolateral membranes of kidney collecting duct, tracheal and colonic epithelia, and in brain pia mater. We report here an extensive immunolocalization study of MIWC and GLIP in non-epithelial and glandular epithelial tissues in rat. Immunogold electron microscopy confirmed colocalization of MIWC and GLIP in basolateral membrane of principal cells in kidney collecting duct. However, in other epithelia, MIWC but not GLIP was expressed in basolateral membrane of parietal cells in stomach, and in excretory tubules of salivary and lacrimal glands; GLIP but not MIWC was expressed in transitional epithelium of urinary bladder and skin epidermis. In the central nervous system, MIWC was strongly expressed in the ependymal layer lining the aqueductal system, and in astrocytes throughout the spinal cord and in selected regions of brain. MIWC was also expressed in a plasma membrane pattern in skeletal, but not smooth or cardiac muscle. Neither protein was expressed in small intestine, testis, liver, spleen and nerve. The tissue-specific expression of MIWC suggests a role in fluid transport and/or cell volume regulation in stomach and glandular epithelia. The functional role of MIWC expression in the neuromuscular system and of GLIP expression in skin and urinary bladder is uncertain. The specific cellular sites of MIWC expression (astrocytes, trachea, sarcolemma, gastric parietal cells and kidney principal cells) correspond exactly to sites where orthogonal arrays of particles (OAPs) have been visualized by freeze-fracture electron microscopy, suggesting that MIWC may be the OAP protein.
21
Breton, Sylvie, Takeaki Inoue, Mark A. Knepper, and Dennis Brown. "Antigen retrieval reveals widespread basolateral expression of syntaxin 3 in renal epithelia." American Journal of Physiology-Renal Physiology 282, no. 3 (March 1, 2002): F523—F529. http://dx.doi.org/10.1152/ajprenal.00128.2001.
Abstract:
Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins play a key role in docking and fusion of intracellular transport vesicles and may regulate apical and basolateral membrane protein delivery in epithelial cells. In a previous study, syntaxin 3 (a target SNARE) protein was detectable in the kidney only in intercalated cells. We now report a more widespread distribution of syntaxin 3 in a variety of renal epithelial cells after antigen retrieval. Sections of rat kidney were treated with SDS and incubated with antisyntaxin 3 antibodies. Strong basolateral membrane staining was seen in descending and ascending thin limbs of Henle, thick ascending limbs of Henle, the macula densa, distal and connecting tubules, and all cells of the collecting duct including A- and B-intercalated cells. The papillary surface epithelium and the transitional epithelium of the ureter were also stained, but proximal tubules were negative. Western blotting revealed a strong signal at 37 kDa in all regions, and the antigen was restricted to membrane fractions. SDS treatment was not necessary to reveal syntaxin 3 in intercalated cells. These data show that syntaxin 3 might be involved in basolateral trafficking pathways in most renal epithelial cell types. The exclusive basolateral location of syntaxin 3 in situ, however, contrasts with the apical location of this SNARE protein in some kidney epithelial cells in culture.
22
Airik, Merlin, Haley Arbore, Elizabeth Childs, Amy B. Huynh, Yu Leng Phua, Chi Wei Chen, Katherine Aird, et al. "Mitochondrial ROS Triggers KIN Pathogenesis in FAN1-Deficient Kidneys." Antioxidants 12, no. 4 (April 8, 2023): 900. http://dx.doi.org/10.3390/antiox12040900.
Abstract:
Karyomegalic interstitial nephritis (KIN) is a genetic adult-onset chronic kidney disease (CKD) characterized by genomic instability and mitotic abnormalities in the tubular epithelial cells. KIN is caused by recessive mutations in the FAN1 DNA repair enzyme. However, the endogenous source of DNA damage in FAN1/KIN kidneys has not been identified. Here we show, using FAN1-deficient human renal tubular epithelial cells (hRTECs) and FAN1-null mice as a model of KIN, that FAN1 kidney pathophysiology is triggered by hypersensitivity to endogenous reactive oxygen species (ROS), which cause chronic oxidative and double-strand DNA damage in the kidney tubular epithelial cells, accompanied by an intrinsic failure to repair DNA damage. Furthermore, persistent oxidative stress in FAN1-deficient RTECs and FAN1 kidneys caused mitochondrial deficiencies in oxidative phosphorylation and fatty acid oxidation. The administration of subclinical, low-dose cisplatin increased oxidative stress and aggravated mitochondrial dysfunction in FAN1-deficient kidneys, thereby exacerbating KIN pathophysiology. In contrast, treatment of FAN1 mice with a mitochondria-targeted ROS scavenger, JP4-039, attenuated oxidative stress and accumulation of DNA damage, mitigated tubular injury, and preserved kidney function in cisplatin-treated FAN1-null mice, demonstrating that endogenous oxygen stress is an important source of DNA damage in FAN1-deficient kidneys and a driver of KIN pathogenesis. Our findings indicate that therapeutic modulation of kidney oxidative stress may be a promising avenue to mitigate FAN1/KIN kidney pathophysiology and disease progression in patients.
23
Wu, John H., Barry J. Billings, and Daniel F. Balkovetz. "Hepatocyte Growth Factor Alters Renal Epithelial Cell Susceptibility to Uropathogenic Escherichia coli." Journal of the American Society of Nephrology 12, no. 12 (December 2001): 2543–53. http://dx.doi.org/10.1681/asn.v12122543.
Abstract:
ABSTRACT. The urinary tract is frequently the source of Escherichia coli bacteremia. Bacteria from the urinary tract must cross an epithelial layer to enter the bloodstream. Hepatocyte growth factor (HGF) alters the polarity of Madin-Darby canine kidney (MDCK) epithelial cells. The role of cell polarity in determining renal epithelial resistance to Escherichia coli invasion is not well known. A model of polarized and HGF-treated MDCK epithelial cells grown on filters was used to study the role of epithelial cell polarity during the interaction of nonvirulent (XL1-Blue) and uropathogenic (J96) strains of Escherichia coli with renal epithelium. Basolateral exposure of MDCK cells to J96, but not XL1-Blue, resulted in loss of transepithelial resistance (TER), which was due to epithelial cytotoxicity and not degradation of epithelial junctional proteins by bacterial proteases. Apical exposure to both J96 and XL1-Blue did not alter TER. Pretreatment of polarized MDCK cell monolayers with HGF renders the cells sensitive to loss of TER and cytotoxicity by apical exposure to J96. Analysis by confocal microscopy demonstrated that HGF treatment of MDCK cell monolayers also greatly enhances adherence of J96 to the apical surface of the cell monolayer. These data demonstrate that the basolateral surface of polarized epithelia is more susceptible to J96 cytotoxicity. The data also support the hypothesis that processes that alter epithelial cell polarity increase sensitivity of epithelia to bacterial injury and adherence from the apical compartment.
24
Gundersen, D., J. Orlowski, and E. Rodriguez-Boulan. "Apical polarity of Na,K-ATPase in retinal pigment epithelium is linked to a reversal of the ankyrin-fodrin submembrane cytoskeleton." Journal of Cell Biology 112, no. 5 (March 1, 1991): 863–72. http://dx.doi.org/10.1083/jcb.112.5.863.
Abstract:
In striking contrast to most other transporting epithelia (e.g., urinary or digestive systems), where Na,K-ATPase is expressed basolaterally, the retinal pigment epithelium (RPE) cells display Na,K-ATPase pumps on the apical membrane. We report here studies aimed to identify the mechanisms underlying this polarity "reversal" of the RPE Na,K-ATPase. By immunofluorescence on thin frozen sections, both alpha and beta subunits were localized on the apical surface of both freshly isolated rat RPE monolayers and RPE monolayers grown in culture. The polarity of the RPE cell is not completely reversed, however, since aminopeptidase, an apically located protein in kidney epithelia, was also found on the apical surface of RPE cells. We used subunit- and isoform-specific cDNA probes to determine that RPE Na,K-ATPase has the same isoform (alpha 1) as the one found in kidney. Ankyrin and fodrin, proteins of the basolateral membrane cytoskeleton of kidney epithelial cells known to be associated with the Na,K-ATPase (Nelson, W. J., and R. W. Hammerton. 1989. J. Cell Biol. 110:349-357) also displayed a reversed apical localization in RPE and were intimately associated to Na,K-ATPase, as revealed by cross-linking experiments. These results indicate that an entire membrane-cytoskeleton complex is assembled with opposite polarity in RPE cells. We discuss our observations in the context of current knowledge on protein sorting mechanisms in epithelial cells.
25
Spring, Kenneth R., Peter M. Bungay, Jean-Yves Chatton, Bruno Flamion, Carter C. Gibson, and Peter J. Harrist. "Video microscopic measurements of diffusion and flow in cultured kidney cells." Proceedings, annual meeting, Electron Microscopy Society of America 50, no. 1 (August 1992): 420–21. http://dx.doi.org/10.1017/s0424820100122502.
Abstract:
New, optical microscopic techniques were developed to study the composition, fluid flow patterns and restrictions to diffusion in the fluid filled spaces surrounding renal epithelial cells. The prevailing theoretical model for the mechanism of isosmotic fluid transport by epithelia, the standing osmotic gradient hypothesis, predicts gradients in ion composition as well as significant restrictions to the diffusion of small solutes within the lateral intercellular spaces separating epithelial cells. Key questions about the validity of the model arise from uncertainties about the values for the hydraulic water permeability of the cell membranes and the lack of data about the composition of the fluid filling the lateral intercellular spaces. This presentation will describe measurements of the local composition, geometry and diffusion coefficients within lateral intercellular spaces of cultured renal epithelia and in the lumen of isolated, perfused renal tubules.
26
Zhou, Wa, Yan-Xia Chen, Ben Ke, Jia-Ke He, Na Zhu, A.-Fei Zhang, Xiang-Dong Fang, and Wei-Ping Tu. "circPlekha7 suppresses renal fibrosis via targeting miR-493-3p/KLF4." Epigenomics 14, no. 4 (February 2022): 199–217. http://dx.doi.org/10.2217/epi-2021-0370.
Abstract:
Aims: The authors aim to investigate the function of circPlekha7 in renal fibrosis. Methods: Human renal tissues from chronic kidney disease patients, kidney cell line and primary cultured renal tubular epithelial cells were used. TGF-β1-treated human kidney 2 cells/tubular epithelial cells and a unilateral ureteral obstruction mouse model were employed to study renal fibrosis. Results: circPlekha7 was diminished in renal tissues from chronic kidney disease patients and TGF-β1-treated human kidney 2 cells and tubular epithelial cells, while miR-493-3p was upregulated. Overexpression of circPlekha7 or knockdown of miR-493-3p suppressed TGF-β1 induced enhancements on epithelial to mesenchymal transition and fibrogenesis, as well as attenuated renal fibrosis and injury in mice subjected to unilateral ureteral obstruction. circPlekha7 bound with miR-493-3p, which directly targeted KLF4. Conclusion: circPlekha7 inhibits epithelial to mesenchymal transition of renal tubular epithelial cells and fibrosis via targeting miR-493-3p to de-repress KLF4/mitofusin2 expression.
27
Beck, Konstanze, Kimiko Hayashi, Brian Nishiguchi, Olivier Le Saux, Masando Hayashi, and Charles D. Boyd. "The Distribution of Abcc6 in Normal Mouse Tissues Suggests Multiple Functions for this ABC Transporter." Journal of Histochemistry & Cytochemistry 51, no. 7 (July 2003): 887–902. http://dx.doi.org/10.1177/002215540305100704.
Abstract:
We have studied the tissue distribution of Abcc6, a member of the ABC transmembrane transporter subfamily C, in normal C57BL/6 mice. RNase protection assays revealed that although almost all tissues studied contained detectable levels of the mRNA encoding Abcc6, the highest levels of Abcc6 mRNA were found in the liver. In situ hybridization (ISH) demonstrated abundant Abcc6 mRNA in epithelial cells from a variety of tissues, including hepatic parenchymal cells, bile duct epithelia, kidney proximal tubules, mucosa and gland cells of the stomach, intestine, and colon, squamous epithelium of the tongue, corneal epithelium of the eye, keratinocytes of the skin, and tracheal and bronchial epithelium. Furthermore, we detected Abcc6 mRNA in arterial endothelial cells, smooth muscle cells of the aorta and myocardium, in circulating leukocytes, lymphocytes in the thymus and lymph nodes, and in neurons of the brain, spinal cord, and the specialized neurons of the retina. Immunohistochemical analysis using a polyclonal Abcc6 rabbit antibody confirmed the tissue distribution of Abcc6 suggested by our ISH studies and revealed the cellular localization of Abcc6 in the basolateral plasma membrane in the epithelial cells of proximal convoluted tubules in the kidney. Although the function of Abcc6 is unknown, mutations in the human ABCC6 gene result in a heritable disorder of connective tissue called pseudoxanthoma elasticum (PXE). Our results demonstrating the presence of Abcc6 in epithelial and endothelial cells in a variety of tissues, including those tissues affected in PXE patients, suggest a possible role for Abcc6 in the normal assembly of extracellular matrix components. However, the presence of Abcc6 in neurons and leukocytes, two cell populations not associated with connective tissue, also suggests a more complex multifunctional role for Abcc6.
28
Aufderheide, E., R. Chiquet-Ehrismann, and P. Ekblom. "Epithelial-mesenchymal interactions in the developing kidney lead to expression of tenascin in the mesenchyme." Journal of Cell Biology 105, no. 1 (July 1, 1987): 599–608. http://dx.doi.org/10.1083/jcb.105.1.599.
Abstract:
Tenascin, a mesenchymal extracellular matrix glycoprotein, has been implicated in epithelial-mesenchymal interactions during fetal development (Chiquet-Ehrismann, R., E. J. Mackie, C. A. Pearson, T. Sakakura, 1986, Cell, 47:131-139). We have now investigated the expression of tenascin during embryonic development of the mouse kidney. In this system, mesenchymal cells convert into epithelial cells as a result of a tissue interaction. By immunofluorescence, tenascin could not be found in the mesenchyme until kidney tubule epithelial began to form. It then became detectable around condensates and s-shaped bodies, the early stages of tubulogenesis. In an in vitro culture system, tenascin expression by the mesenchyme is tightly coupled to the de novo formation of epithelial, and does not occur if tubulogenesis is suppressed. The results strongly suggest that the formation of the new epithelium stimulates the expression of tenascin in the nearby mesenchyme. During postnatal development, the expression of tenascin decreases and the spatial distribution changes. In kidneys from adult mice, no tenascin can be found in the cortex, but interspersed patches of staining are visible in the medullary stroma. The results strongly support the view that tenascin is involved in epithelial-mesenchymal interactions. It could therefore be crucial for embryonic development.
29
Quaggin, S. E., L. Schwartz, S. Cui, P. Igarashi, J. Deimling, M. Post, and J. Rossant. "The basic-helix-loop-helix protein pod1 is critically important for kidney and lung organogenesis." Development 126, no. 24 (December 15, 1999): 5771–83. http://dx.doi.org/10.1242/dev.126.24.5771.
Abstract:
Epithelial-mesenchymal interactions are required for the development of all solid organs but few molecular mechanisms that underlie these interactions have been identified. Pod1 is a basic-helix-loop-helix (bHLH) transcription factor that is highly expressed in the mesenchyme of developing organs that include the lung, kidney, gut and heart and in glomerular visceral epithelial cells (podocytes). To determine the function of Pod1 in vivo, we have generated a lacZ-expressing null Pod1 allele. Null mutant mice are born but die in the perinatal period with severely hypoplastic lungs and kidneys that lack alveoli and mature glomeruli. Although Pod1 is exclusively expressed in the mesenchyme and podocytes, major defects are observed in the adjacent epithelia and include abnormalities in epithelial differentiation and branching morphogenesis. Pod1 therefore appears to be essential for regulating properties of the mesenchyme that are critically important for lung and kidney morphogenesis. Defects specific to later specialized cell types where Pod1 is expressed, such as the podocytes, were also observed, suggesting that this transcription factor may play multiple roles in kidney morphogenesis.
30
Ichimura, T., J. A. Maier, T. Maciag, G. Zhang, and J. L. Stevens. "FGF-1 in normal and regenerating kidney: expression in mononuclear, interstitial, and regenerating epithelial cells." American Journal of Physiology-Renal Physiology 269, no. 5 (November 1, 1995): F653—F662. http://dx.doi.org/10.1152/ajprenal.1995.269.5.f653.
Abstract:
The proximal tubule epithelium regenerates following nephrotoxic damage. To determine the role of fibroblast growth factors (FGFs) in the regeneration of rat proximal tubule epithelial (RPTE) cells, we investigated proliferation, differentiation, and FGF-1 expression in vivo in rat kidney before and after nephrotoxic damage to the proximal tubule epithelium caused by S-(1,1,2,2-tetrafluoroethyl)-L-cysteine administration. In undamaged kidneys, FGF-1 was expressed in distal tubule elements, including cortical and medullary collecting ducts, as well as in blood vessels and glomeruli, but was absent in RPTE. One day after damage, there was an increase in proliferation of surviving proximal tubule epithelial cells and a coincident increase in FGF-1 expression in invading mononuclear cells. After this initial burst of proliferation, FGF-1 expression increased in poorly differentiated vimentin-positive regenerative epithelial cells, indicating that autocrine FGF-1 expression in the regenerative epithelium is a later event in the regeneration process. FGF-1 staining persisted in foci of macrophages, interstitial cells, and nephropathic tubules within areas of interstitial expansion 2 wk after damage. We concluded that transient paracrine and autocrine expression of FGF-1 could play mitogenic and/or morphogenic roles during tubular regeneration. Persistent expression in macrophages, fibroblasts, and nephropathic tubules may be associated with tubular degeneration. FGF-1 expression may be an important contributor to both tubular regeneration and degenerative disease following toxicant exposure.
31
SULLIVAN, LAWRENCE P., DARREN P. WALLACE, and JARED J. GRANTHAM. "Epithelial Transport in Polycystic Kidney Disease." Physiological Reviews 78, no. 4 (October 1, 1998): 1165–91. http://dx.doi.org/10.1152/physrev.1998.78.4.1165.
Abstract:
Sullivan, Lawrence P., Darren P. Wallace, and Jared J. Grantham. Epithelial Transport in Polycystic Kidney Disease. Physiol. Rev. 78: 1165–1191, 1998. — In autosomal dominant polycystic kidney disease (ADPKD), the genetic defect results in the slow growth of a multitude of epithelial cysts within the renal parenchyma. Cysts originate within the glomeruli and all tubular structures, and their growth is the result of proliferation of incompletely differentiated epithelial cells and the accumulation of fluid within the cysts. The majority of cysts disconnect from tubular structures as they grow but still accumulate fluid within the lumen. The fluid accumulation is the result of secretion of fluid driven by active transepithelial Cl− secretion. Proliferation of the cells and fluid secretion are activated by agonists of the cAMP signaling pathway. The transport mechanisms involved include the cystic fibrosis transmembrane conductance regulator (CFTR) present in the apical membrane of the cystic cells and a bumetanide-sensitive transporter located in the basolateral membrane. A lipid factor, called cyst activating factor, has been found in the cystic fluid. Cyst activating factor stimulates cAMP production, proliferation, and fluid secretion by cultured renal epithelial cells and also is a chemotactic agent. Cysts also appear in the intrahepatic biliary tree in ADPKD. Normal ductal cells secrete Cl− and HCO− 3. The cystic ductal cell also secretes Cl−, but HCO− 3 secretion is diminished, probably as the result of a lower population of Cl−/HCO− 3 exchangers in the apical membrane as compared with the normal cells. Some segments of the normal renal tubule are also capable of utilizing CFTR to secrete Cl−, particularly the inner medullary collecting duct. The ability of Madin-Darby canine kidney cells and normal human kidney cortex cells to form cysts in culture and to secrete fluid and the functional similarities between these incompletely differentiated, proliferative cells and developing cells in the intestinal crypt and in the fetal lung have led us to suggest that Cl− and fluid secretion may be a common property of at least some renal epithelial cells in an intermediate stage of development. The genetic defect in ADPKD may not directly affect membrane transport mechanisms but rather may arrest the development of certain renal epithelial cells in an incompletely differentiated, proliferative stage.
32
Xu, Zheng, Wu Luo, Lingfeng Chen, Zaishou Zhuang, Daona Yang, Jianchang Qian, Zia A. Khan, et al. "Ang II (Angiotensin II)–Induced FGFR1 (Fibroblast Growth Factor Receptor 1) Activation in Tubular Epithelial Cells Promotes Hypertensive Kidney Fibrosis and Injury." Hypertension 79, no. 9 (September 2022): 2028–41. http://dx.doi.org/10.1161/hypertensionaha.122.18657.
Abstract:
Background: Elevated Ang II (angiotensin II) level leads to a range of conditions, including hypertensive kidney disease. Recent evidences indicate that FGFR1 (fibroblast growth factor receptor 1) signaling may be involved in kidney injuries. In this study, we determined whether Ang II alters FGFR1 signaling to mediate renal dysfunction. Methods: Human archival kidney samples from patients with or without hypertension were examined. Multiple genetic and pharmacological approaches were used to investigate FGFR1-mediated signaling in tubular epithelial NRK-52E cells in response to Ang II stimulation. C57BL/6 mice were infused with Ang II for 28 days to develop hypertensive kidney disease. Mice were treated with either adeno-associated virus expressing FGFR1 shRNA or FGFR1 inhibitor AZD4547. Results: Kidney specimens from subjects with hypertension and mice challenged with Ang II have increased FGFR1 activity in renal epithelial cells. Renal epithelial cells in culture initiate extracellular matrix programming in response to Ang II, through the activation of FGFR1, which is independent of both AT1R (angiotensin II receptor type 1) and AT2R (angiotensin II receptor type 2). The RNA sequencing analysis indicated that disrupting FGFR1 suppresses Ang II–induced fibrogenic responses in epithelial cells. Mechanistically, Ang II–activated FGFR1 leads to STAT3 (signal transducer and activator of transcription 3) activation, which is responsible for fibrogenic factor expression in kidneys. In the mouse model of hypertensive kidney disease, genetic knockdown of FGFR1 or pharmacological inhibition of its activity protected kidneys from dysfunction and fibrosis upon Ang II challenge. Conclusions: Our studies uncover a novel mechanism causing renal fibrosis in hypertension and indicate FGFR1 as a potential target to preserve renal function and integrity.
33
Amura, Claudia R., Kelley S. Brodsky, Berenice Gitomer, Kim McFann, Gwendal Lazennec, Matthew T. Nichols, Alkesh Jani, Robert W. Schrier, and R. Brian Doctor. "CXCR2 agonists in ADPKD liver cyst fluids promote cell proliferation." American Journal of Physiology-Cell Physiology 294, no. 3 (March 2008): C786—C796. http://dx.doi.org/10.1152/ajpcell.00457.2007.
Abstract:
Autosomal dominant polycystic kidney disease (ADPKD) is a highly prevalent genetic disease that results in cyst formation in kidney and liver. Cytokines and growth factors secreted by the cyst-lining epithelia are positioned to initiate autocrine/paracrine signaling and promote cyst growth. Comparative analyses of human kidney and liver cyst fluids revealed disparate cytokine/growth factor profiles. CXCR2 agonists, including IL-8, epithelial neutrophil-activating peptide (ENA-78), growth-related oncogene-α (GRO-α), are potent proliferative agents that were found at high levels in liver but not kidney cyst fluids. Liver cysts are lined by epithelial cells derived from the intrahepatic bile duct (i.e., cholangiocytes). In polarized pkd2(WS25/−) mouse liver cyst epithelial monolayers, CXCR2 agonists were released both apically and basally, indicating that they may act both on the endothelial and epithelial cells within or lining the cyst wall. IL-8 and human liver cyst fluid induced cell proliferation of HMEC-1 cells, a human microvascular endothelial cell line, and Mz-ChA1 cells, a human cholangiocyte cell model. IL-8 expression can be regulated by specific stresses. Hypoxia and mechanical stretch, two likely stressors acting on the liver cyst epithelia, significantly increased IL-8 secretion and promoter activity. AP-1, c/EBP, and NF-κB were required but not sufficient to drive the stress-induced increase in IL-8 transcription. An upstream element between −272 and −1,481 bp allowed for the stress-induced increase in IL-8 transcription. These studies support the hypothesis that CXCR2 signaling promotes ADPKD liver cyst growth.
34
Huling, Jennifer C., Trairak Pisitkun, Jae H. Song, Ming-Jiun Yu, Jason D. Hoffert, and Mark A. Knepper. "Gene expression databases for kidney epithelial cells." American Journal of Physiology-Renal Physiology 302, no. 4 (February 15, 2012): F401—F407. http://dx.doi.org/10.1152/ajprenal.00457.2011.
Abstract:
The 21st century has seen an explosion of new high-throughput data from transcriptomic and proteomic studies. These data are highly relevant to the design and interpretation of modern physiological studies but are not always readily accessible to potential users in user-friendly, searchable formats. Data from our own studies involving transcriptomic and proteomic profiling of renal tubule epithelia have been made available on a variety of online databases. Here, we provide a roadmap to these databases and illustrate how they may be useful in the design and interpretation of physiological studies. The databases can be accessed through http://helixweb.nih.gov/ESBL/Database .
35
Elfving, P., P. Aman, N. Mandahl, R. Lundgren, and F. Mitelman. "Trisomy 7 in nonneoplastic epithelial kidney cells." Cytogenetic and Genome Research 69, no. 1-2 (1995): 90–96. http://dx.doi.org/10.1159/000133945.
36
Kwak, Sungwook, Ji-Eun Jung, Xun Jin, Sun-Myung Kim, Tae-Kyung Kim, Joong-Seob Lee, Soo-Yeon Lee, et al. "Establishment of Immortal Swine Kidney Epithelial Cells." Animal Biotechnology 17, no. 1 (July 2006): 51–58. http://dx.doi.org/10.1080/10495390500461070.
37
Pizzuti, Valeria, Chiara Donadei, Emma Balducelli, Diletta Conte, Elisa Gessaroli, Francesca Paris, Claudia Bini, et al. "Urine-Derived Renal Epithelial Cells (URECs) from Transplanted Kidneys as a Promising Immunomodulatory Cell Population." Cells 12, no. 12 (June 15, 2023): 1630. http://dx.doi.org/10.3390/cells12121630.
Abstract:
Kidney transplantation is a lifesaving procedure for patients with end-stage kidney disease (ESKD). Organs derived from donation after cardiac death (DCD) are constantly increasing; however, DCD often leads to ischaemia-reperfusion (IR) and Acute Kidney Injury (AKI) events. These phenomena increase kidney cell turnover to replace damaged cells, which are voided in urine. Urine-derived renal epithelial cells (URECs) are rarely present in the urine of healthy subjects, and their loss has been associated with several kidney disorders. The present study aimed to characterize the phenotype and potential applications of URECs voided after transplant. The results indicate that URECs are highly proliferating cells, expressing several kidney markers, including markers of kidney epithelial progenitor cells. Since the regulation of the immune response is crucial in organ transplantation and new immunoregulatory strategies are needed, UREC immunomodulatory properties were investigated. Co-culture with peripheral blood mononuclear cells (PBMCs) revealed that URECs reduced PBMC apoptosis, inhibited lymphocyte proliferation, increased T regulatory (Treg) cells and reduced T helper 1 (Th1) cells. URECs from transplanted patients represent a promising cell source for the investigation of regenerative processes occurring in kidneys, and for cell-therapy applications based on the regulation of the immune response.
38
Liu, Katy C., Damon T. Jacobs, Brian D. Dunn, Alan S. Fanning, and Richard E. Cheney. "Myosin-X functions in polarized epithelial cells." Molecular Biology of the Cell 23, no. 9 (May 2012): 1675–87. http://dx.doi.org/10.1091/mbc.e11-04-0358.
Abstract:
Myosin-X (Myo10) is an unconventional myosin that localizes to the tips of filopodia and has critical functions in filopodia. Although Myo10 has been studied primarily in nonpolarized, fibroblast-like cells, Myo10 is expressed in vivo in many epithelia-rich tissues, such as kidney. In this study, we investigate the localization and functions of Myo10 in polarized epithelial cells, using Madin-Darby canine kidney II cells as a model system. Calcium-switch experiments demonstrate that, during junction assembly, green fluorescent protein–Myo10 localizes to lateral membrane cell–cell contacts and to filopodia-like structures imaged by total internal reflection fluorescence on the basal surface. Knockdown of Myo10 leads to delayed recruitment of E-cadherin and ZO-1 to junctions, as well as a delay in tight junction barrier formation, as indicated by a delay in the development of peak transepithelial electrical resistance (TER). Although Myo10 knockdown cells eventually mature into monolayers with normal TER, these monolayers do exhibit increased paracellular permeability to fluorescent dextrans. Importantly, knockdown of Myo10 leads to mitotic spindle misorientation, and in three-dimensional culture, Myo10 knockdown cysts exhibit defects in lumen formation. Together these results reveal that Myo10 functions in polarized epithelial cells in junction formation, regulation of paracellular permeability, and epithelial morphogenesis.
39
Djudjaj, Sonja, Panagiotis Kavvadas, Niki Prakoura, Roman D. Bülow, Tiffany Migeon, Sandrine Placier, Christos E. Chadjichristos, Peter Boor, and Christos Chatziantoniou. "Activation of Notch3 in Renal Tubular Cells Leads to Progressive Cystic Kidney Disease." International Journal of Molecular Sciences 23, no. 2 (January 14, 2022): 884. http://dx.doi.org/10.3390/ijms23020884.
Abstract:
Background: Polycystic kidney disease (PKD) is a genetic disorder affecting millions of people worldwide that is characterized by fluid-filled cysts and leads to end-stage renal disease (ESRD). The hallmarks of PKD are proliferation and dedifferentiation of tubular epithelial cells, cellular processes known to be regulated by Notch signaling. Methods: We found increased Notch3 expression in human PKD and renal cell carcinoma biopsies. To obtain insight into the underlying mechanisms and the functional consequences of this abnormal expression, we developed a transgenic mouse model with conditional overexpression of the intracellular Notch3 (ICN3) domain specifically in renal tubules. We evaluated the alterations in renal function (creatininemia, BUN) and structure (cysts, fibrosis, inflammation) and measured the expression of several genes involved in Notch signaling and the mechanisms of inflammation, proliferation, dedifferentiation, fibrosis, injury, apoptosis and regeneration. Results: After one month of ICN3 overexpression, kidneys were larger with tubules grossly enlarged in diameter, with cell hypertrophy and hyperplasia, exclusively in the outer stripe of the outer medulla. After three months, mice developed numerous cysts in proximal and distal tubules. The cysts had variable sizes and were lined with a single- or multilayered, flattened, cuboid or columnar epithelium. This resulted in epithelial hyperplasia, which was observed as protrusions into the cystic lumen in some of the renal cysts. The pre-cystic and cystic epithelium showed increased expression of cytoskeletal filaments and markers of epithelial injury and dedifferentiation. Additionally, the epithelium showed increased proliferation with an aberrant orientation of the mitotic spindle. These phenotypic tubular alterations led to progressive interstitial inflammation and fibrosis. Conclusions: In summary, Notch3 signaling promoted tubular cell proliferation, the alignment of cell division, dedifferentiation and hyperplasia, leading to cystic kidney diseases and pre-neoplastic lesions.
40
Ziegler, Wolfgang H., Birga Soetje, Lisa P. Marten, Jana Wiese, Mithila Burute, and Dieter Haffner. "Fibrocystin Is Essential to Cellular Control of Adhesion and Epithelial Morphogenesis." International Journal of Molecular Sciences 21, no. 14 (July 20, 2020): 5140. http://dx.doi.org/10.3390/ijms21145140.
Abstract:
Mutations of the Pkhd1 gene cause autosomal recessive polycystic kidney disease (ARPKD). Pkhd1 encodes fibrocystin/polyductin (FPC), a ciliary type I membrane protein of largely unknown function, suggested to affect adhesion signaling of cells. Contributions of epithelial cell adhesion and contractility to the disease process are elusive. Here, we link loss of FPC to defective epithelial morphogenesis in 3D cell culture and altered cell contact formation. We study Pkhd1-silenced Madin-Darby Canine Kidney II (MDCKII) cells using an epithelial morphogenesis assay based on micropatterned glass coverslips. The assay allows analysis of cell adhesion, polarity and lumen formation of epithelial spheroids. Pkhd1 silencing critically affects the initial phase of the morphogenesis assay, leading to a reduction of correctly polarized spheroids by two thirds. Defects are characterized by altered cell adhesion and centrosome positioning of FPC-deficient cells in their 1-/2-cell stages. When myosin II inhibitor is applied to reduce cellular tension during the critical early phase of the assay, Pkhd1 silencing no longer inhibits formation of correctly polarized epithelia. We propose that altered sensing and cell interaction of FPC-deficient epithelial cells promote progressive epithelial defects in ARPKD.
41
Bondue, Tjessa, Fanny O. Arcolino, Koenraad R. P. Veys, Oyindamola C. Adebayo, Elena Levtchenko, Lambertus P. van den Heuvel, and Mohamed A. Elmonem. "Urine-Derived Epithelial Cells as Models for Genetic Kidney Diseases." Cells 10, no. 6 (June 6, 2021): 1413. http://dx.doi.org/10.3390/cells10061413.
Abstract:
Epithelial cells exfoliated in human urine can include cells anywhere from the urinary tract and kidneys; however, podocytes and proximal tubular epithelial cells (PTECs) are by far the most relevant cell types for the study of genetic kidney diseases. When maintained in vitro, they have been proven extremely valuable for discovering disease mechanisms and for the development of new therapies. Furthermore, cultured patient cells can individually represent their human sources and their specific variants for personalized medicine studies, which are recently gaining much interest. In this review, we summarize the methodology for establishing human podocyte and PTEC cell lines from urine and highlight their importance as kidney disease cell models. We explore the well-established and recent techniques of cell isolation, quantification, immortalization and characterization, and we describe their current and future applications.
42
Zumbrun, Steven D., Leanne Hanson, James F. Sinclair, James Freedy, Angela R. Melton-Celsa, Jaime Rodriguez-Canales, Jeffrey C. Hanson, and Alison D. O'Brien. "Human Intestinal Tissue and Cultured Colonic Cells Contain Globotriaosylceramide Synthase mRNA and the Alternate Shiga Toxin Receptor Globotetraosylceramide." Infection and Immunity 78, no. 11 (August 23, 2010): 4488–99. http://dx.doi.org/10.1128/iai.00620-10.
Abstract:
ABSTRACT Escherichia coli O157:H7 and other Shiga toxin (Stx)-producing E. coli (STEC) bacteria are not enteroinvasive but can cause hemorrhagic colitis. In some STEC-infected individuals, a life-threatening sequela of infection called the hemolytic uremic syndrome may develop that can lead to kidney failure. This syndrome is linked to the production of Stx by the infecting organism. For Stx to reach the kidney, the toxin must first penetrate the colonic epithelial barrier. However, the Stx receptor, globotriaosylceramide (Gb3), has been thought to be absent from human intestinal epithelial cells. Thus, the mechanisms by which the toxin associates with and traverses through the intestine en route to the kidneys have been puzzling aspects of STEC pathogenesis. In this study, we initially determined that both types of Stx made by STEC, Stx1 and Stx2, do in fact bind to colonic epithelia in fresh tissue sections and to a colonic epithelial cell line (HCT-8). We also discovered that globotetraosylceramide (Gb4), a lower-affinity toxin receptor derived from Gb3, is readily detectable on the surfaces of human colonic tissue sections and HCT-8 cells. Furthermore, we found that Gb3 is present on a fraction of HCT-8 cells, where it presumably functions to bind and internalize Stx1 and Stx2. In addition, we established by quantitative real-time PCR (qRT-PCR) that both fresh colonic epithelial sections and HCT-8 cells express Gb3 synthase mRNA. Taken together, our data suggest that Gb3 may be present in small quantities in human colonic epithelia, where it may compete for Stx binding with the more abundantly expressed glycosphingolipid Gb4.
43
Cohen, David, Patrick J. Brennwald, Enrique Rodriguez-Boulan, and Anne Müsch. "Mammalian PAR-1 determines epithelial lumen polarity by organizing the microtubule cytoskeleton." Journal of Cell Biology 164, no. 5 (February 23, 2004): 717–27. http://dx.doi.org/10.1083/jcb.200308104.
Abstract:
Epithelial differentiation involves the generation of luminal surfaces and of a noncentrosomal microtubule (MT) network aligned along the polarity axis. Columnar epithelia (e.g., kidney, intestine, and Madin-Darby canine kidney [MDCK] cells) generate apical lumina and orient MT vertically, whereas liver epithelial cells (hepatocytes and WIFB9 cells) generate lumina at cell–cell contact sites (bile canaliculi) and orient MTs horizontally. We report that knockdown or inhibition of the mammalian orthologue of Caenorhabditis elegans Par-1 (EMK1 and MARK2) during polarization of cultured MDCK and WIFB9 cells prevented development of their characteristic lumen and nonradial MT networks. Conversely, EMK1 overexpression induced the appearance of intercellular lumina and horizontal MT arrays in MDCK cells, making EMK1 the first known candidate to regulate the developmental branching decision between hepatic and columnar epithelial cells. Our experiments suggest that EMK1 primarily promotes reorganization of the MT network, consistent with the MT-regulating role of this gene product in other systems, which in turn controls lumen formation and position.
44
Myszczyszyn, Adam, Oliver Popp, Severine Kunz, Anje Sporbert, Simone Jung, Louis C. Penning, Annika Fendler, Philipp Mertins, and Walter Birchmeier. "Mice with renal-specific alterations of stem cell-associated signaling develop symptoms of chronic kidney disease but surprisingly no tumors." PLOS ONE 19, no. 3 (March 21, 2024): e0282938. http://dx.doi.org/10.1371/journal.pone.0282938.
Abstract:
Previously, we found that Wnt and Notch signaling govern stem cells of clear cell kidney cancer (ccRCC) in patients. To mimic stem cell responses in the normal kidney in vitro in a marker-unbiased fashion, we have established tubular organoids (tubuloids) from total single adult mouse kidney epithelial cells in Matrigel and serum-free conditions. Deep proteomic and phosphoproteomic analyses revealed that tubuloids resembled renewal of adult kidney tubular epithelia, since tubuloid cells displayed activity of Wnt and Notch signaling, long-term proliferation and expression of markers of proximal and distal nephron lineages. In our wish to model stem cell-derived human ccRCC, we have generated two types of genetic double kidney mutants in mice: Wnt-β-catenin-GOF together with Notch-GOF and Wnt-β-catenin-GOF together with a most common alteration in ccRCC, Vhl-LOF. An inducible Pax8-rtTA-LC1-Cre was used to drive recombination specifically in adult kidney epithelial cells. We confirmed mutagenesis of β-catenin, Notch and Vhl alleles on DNA, protein and mRNA target gene levels. Surprisingly, we observed symptoms of chronic kidney disease (CKD) in mutant mice, but no increased proliferation and tumorigenesis. Thus, the responses of kidney stem cells in the tubuloid and genetic systems produced different phenotypes, i.e. enhanced renewal versus CKD.
45
Hernando, N., S. Sheikh, Z. Karim-Jimenez, H. Galliker, J. Forgo, J. Biber, and H. Murer. "Asymmetrical targeting of type II Na-Picotransporters in renal and intestinal epithelial cell lines." American Journal of Physiology-Renal Physiology 278, no. 3 (March 1, 2000): F361—F368. http://dx.doi.org/10.1152/ajprenal.2000.278.3.f361.
Abstract:
Targeting of newly synthesized transporters to either the apical or basolateral domains of polarized cells is crucial for the function of epithelia, such as in the renal proximal tubule or in the small intestine. Recently, different sodium-phosphate cotransporters have been identified. Type II cotransporters can be subdivided into two groups: type IIa and type IIb. Type IIa is predominantly expressed in renal proximal tubules, whereas type IIb is located on the intestinal and lung epithelia. To gain some insights into the polarized targeting of the type II cotransporters, we have transiently expressed type IIa and type IIb cotransporters in several epithelial cell lines: two lines derived from renal proximal cells (opossum kidney and LLC-PK1), one from renal distal cells (Madin-Darby canine kidney), and one from colonic epithelium (CaCo-2). We studied the expression of the transporters fused to the enhanced green fluorescent protein. Our data indicate that the polarized targeting is dependent on molecular determinants most probably located at the COOH terminus of the cotransporters as well as on the cellular context.
46
Párducz, A., E. Dobó, J. R. Wolff, P. Petrusz, and S. L. Erdö. "GABA-immunoreactive structures in rat kidney." Journal of Histochemistry & Cytochemistry 40, no. 5 (May 1992): 675–80. http://dx.doi.org/10.1177/40.5.1573248.
Abstract:
We examined the distribution of gamma-aminobutyric acid-like immunoreactivity (GABA-LI) in the rat kidney by light and electron microscopy. In vibratome sections, GABA-LI was present in both the renal medulla and cortex. The inner stripe of the outer medulla was most heavily and almost homogeneously labeled, whereas GABA-LI in the cortex was mainly confined only to some tubules. GABA-positive structures involved the epithelial cells of the thin and the thick ascending limbs of the loop of Henle, the connecting tubules, and the collecting ducts. In GABA-positive connecting tubules and collecting ducts the immunoreactivity was present in the cytoplasm of about half of the epithelial cells. As revealed by electron microscopy, the labeled cells in the collecting tubules were the light (principal) cells. No GABA-LI occurred in neuronal structures. These findings are consistent with the presence of a non-neuronal GABA system in the rat kidney. Furthermore, the specific distribution of GABA in the tubular epithelium suggests a functional significance of this amino acid in tubular transport processes.
47
Ichimura, T., P. W. Finch, G. Zhang, M. Kan, and J. L. Stevens. "Induction of FGF-7 after kidney damage: a possible paracrine mechanism for tubule repair." American Journal of Physiology-Renal Physiology 271, no. 5 (November 1, 1996): F967—F976. http://dx.doi.org/10.1152/ajprenal.1996.271.5.f967.
Abstract:
A member of the fibroblast growth factor (FGF) family, keratinocyte growth factor (FGF-7 has unique specificity for epithelial cells. We investigated the role of FGF-7 in repair of proximal tubular damage caused by S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (TFEC). In situ hybridization localized FGF-7 to interstitial cells in the medulla and outer stripe of the outer medulla. Interstitial FGF-7 expression increased throughout the kidney 1 day after TFEC treatment. FGFR2 IIIb mRNA was high in the papilla and medulla and also increased after TFEC administration. By in situ hybridization, FGFR2 IIIb was localized to the tubular epithelium, particularly in collecting ducts. Proliferation of collecting duct epithelial cells increased in adult kidney after damage to the proximal tubule. FGFR2 IIIb, but not FGF-7, mRNA was also expressed by rat proximal tubule epithelial (RPTE) cells in vitro, and FGF-7 increased DNA synthesis in RPTE. Thus FGFR2 IIIb and FGF-7 expression is segregated between epithelial and interstitial cells forming a paracrine growth factor loop. These results raise the possibility that a novel paracrine growth loop is activated by chemical damage and regulates epithelial cell growth during tubular repair.
48
Schafer, D. A., M. S. Mooseker, and J. A. Cooper. "Localization of capping protein in chicken epithelial cells by immunofluorescence and biochemical fractionation." Journal of Cell Biology 118, no. 2 (July 15, 1992): 335–46. http://dx.doi.org/10.1083/jcb.118.2.335.
Abstract:
We have localized capping protein in epithelial cells of several chicken tissues using affinity-purified polyclonal antibodies and immunofluorescence. Capping protein has a distribution in each tissue coincident with proteins of the cell-cell junctional complex, which includes the zonula adherens, zonula occludens, and desmosome. "En face" views of the epithelial cells showed capping protein distributed in a polygonal pattern coincident with cell boundaries in intestinal epithelium, sensory epithelium of the cochlea, and the pigmented epithelium of the retina and at regions of cell-cell contact between chick embryo kidney cells in culture. "Edge-on" views obtained by confocal microscopy of intact single intestinal epithelial cells and of retinal pigmented epithelium showed that capping protein is located in the apical region of the epithelial cells coincident with the junctional complexes. These images do not resolve the individual types of junctions of the junctional complex. Immunolabeling of microvilli or stereocilia was faint or not detectable. Capping protein was also detected in the cytoplasm of intact intestinal epithelial cells and in nuclei of cells in the pigmented retina and in the kidney cell cultures, but not in nuclei of cells of the intestinal epithelium or sensory epithelium. Biochemical fractionation of isolated intestinal epithelial cells shows capping protein in the brush border fraction, which contains the junctional complexes, and in the soluble fraction. These results are consistent with the results of the immunolabeling experiments. Highly purified microvilli of the brush borders also contained capping protein; this result was unexpected based on the low intensity of immunofluorescence staining of microvilli and stereocilia. The microvilli were not contaminated with junctional complexes, as defined by the absence of several markers for cell junctions. The cause and significance of this discrepancy is not certain at this time. Since capping protein binds the barbed end of actin filaments in vitro, we hypothesize that capping protein is bound to the barbed ends of actin filaments associated with one or more of the junctions of the junctional complex.
49
Sandegaard, Samuel Loft, Andreas Riishede, Henrik Birn, Helle Hasager Damkier, and Jeppe Praetorius. "The Cyst Epithelium in Polycystic Kidney Disease Patients Displays Normal Apical-Basolateral Cell Polarity." International Journal of Molecular Sciences 25, no. 3 (February 5, 2024): 1904. http://dx.doi.org/10.3390/ijms25031904.
Abstract:
The main characteristic of polycystic kidney disease is the development of multiple fluid-filled renal cysts. The discovery of mislocalized sodium-potassium pump (Na,K-ATPase) in the apical membrane of cyst-lining epithelia alluded to reversal of polarity as a possible explanation for the fluid secretion. The topic of apical Na,K-ATPase in cysts remains controversial. We investigated the localization of the Na,K-ATPase and assessed the apical-basolateral polarization of cyst-lining epithelia by means of immunohistochemistry in kidney tissue from six polycystic kidney disease patients undergoing nephrectomy. The Na,K-ATPase α1 subunit was conventionally situated in the basolateral membrane of all immunoreactive cysts. Proteins of the Crumbs and partitioning defective (Par) complexes were localized to the apical membrane domain in cyst epithelial cells. The apical targeting protein Syntaxin-3 also immunolocalized to the apical domain of cyst-lining epithelial cells. Proteins of the basolateral Scribble complex immunolocalized to the basolateral domain of cysts. Thus, no deviations from the typical epithelial distribution of basic cell polarity proteins were observed in the cysts from the six patients. Furthermore, we confirmed that cysts can originate from virtually any tubular segment with preserved polarity. In conclusion, we find no evidence of a reversal in apical-basolateral polarity in cyst-lining epithelia in polycystic kidney disease.
50
Nadasdy, T., Z. Laszik, G. Lajoie, K. E. Blick, D. E. Wheeler, and F. G. Silva. "Proliferative activity of cyst epithelium in human renal cystic diseases." Journal of the American Society of Nephrology 5, no. 7 (January 1995): 1462–68. http://dx.doi.org/10.1681/asn.v571462.
Abstract:
Increased proliferative activity of the renal tubular epithelium is thought to be a prerequisite for renal cyst formation by many investigators. However, in humans, the exact in vivo proliferation rate of epithelial cells lining these cysts is not known. In this study, which used immunohistochemical methods with an antibody to proliferating cell nuclear antigen (PCNA), the proliferation index (PI) (percentage of PCNA positive cell nuclei among epithelial cells lining the renal cysts) was determined in 10 cases of autosomal dominant polycystic kidney disease (ADPKD), 8 cases of autosomal recessive polycystic kidney disease (ARPKD), and 8 cases of acquired cystic kidney disease (ACKD). Cysts with proximal and distal nephron phenotype and cysts with markedly thickened basement membranes, as well as cysts lined by atrophic (flattened), "regular" (cuboidal or cylindrical), and hyperplastic epithelium, were evaluated separately. The overall PI of cyst epithelium (excluding hyperplastic cysts) was 2.58 in ADPKD, was 10.5 in ARPKD, and was 3.61 in ACKD. Overall, there were only minor differences in the PI between the various types of cysts. Cysts with hyperplastic epithelium in ACKD (unlike in ADPKD) showed a high PI (9.1). For comparison, the PI of two renal cell carcinomas occurring in two ACKD cases was also determined (13.70 and 8.67%). The PI of tubular epithelium in normal kidneys was only 0.22 to 0.33%, depending on the tubule segment. In contrast, in polycystic kidneys, those noncystic segments of the nephron from which the cysts are thought to originate (distal nephron (specifically collecting duct)) in ARPKD, primarily distal in ADPKD, proximal and distal in ACKD, had PI values similar to those of the cyst epithelium.(ABSTRACT TRUNCATED AT 400 WORDS)