Academic literature on the topic 'Extracellular Matrix FCP'
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Journal articles on the topic "Extracellular Matrix FCP"
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Strilakou, Athina, Apostolos Perelas, Andreas Lazaris, Asteria Papavdi, Petros Karkalousos, Ioanna Giannopoulou, Anastasios Kriebardis, Ioannis Panayiotides, and Charis Liapi. "Immunohistochemical determination of the extracellular matrix modulation in a rat model of choline-deprived myocardium: the effects of carnitine." Fundamental & Clinical Pharmacology 30, no. 1 (December 8, 2015): 47–57. http://dx.doi.org/10.1111/fcp.12163.
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Xiao, Zebin, Leslie A. Hopper, Meghan C. Kopp, Emily McMillan, Yue Li, Richard L. Barrett, and Ellen Puré. "Abstract C009: Disruption of tumor-promoting desmoplasia by adoptive transfer of fibroblast activation protein targeted chimeric antigen receptor (CAR) T cells enhances anti-tumor immunity and immunotherapy." Cancer Research 82, no. 22_Supplement (November 15, 2022): C009. http://dx.doi.org/10.1158/1538-7445.panca22-c009.
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Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease due to the poor response to current therapeutic treatments. A major barrier to effective treatment of PDAC is the extensive remodeling of tumor stroma characterized by accumulation of cancer associated fibroblasts (CAFs) and extracellular matrix which forms a physical barrier that limits access of the drugs to the cancer cells, suppresses the immune system, and attenuates efficacy of immunotherapies. Fibroblast activation protein (FAP) is highly expressed in a pro-tumorigenic subset of CAFs in PDAC. We hypothesized that depletion of FAP+-CAFs would deplete extracellular matrix (ECM) and reduce the immune suppressive function of the stroma and thereby enhance the efficacy of tumor antigen targeted CAR T cell therapy in PDAC. Using real-time tumor fragment-based 2-photon microscopy, multiparametric flow cytometry and multiplexed immunofluorescence staining, we showed that FAP targeted CAR T cells (FAP-CAR T) efficiently traffic into tumors compared with tumor-antigen (mesothelin) targeted CAR (Meso-CAR) T cells which were trapped in the stroma-rich or matrix-dense areas and led to depletion of immunosuppressive FAP+ cells and reprogrammed the fibrillar collagen network surrounding tumor nests, advancing the infiltration of FAP-CAR T cells into tumor nests. Strikingly, FAP-CAR T cell-mediated depletion for FAP+ cells also rendered the tumor microenvironment permissive to the infiltration and anti-tumor activity of tumor antigen meso-CAR T cells. Moreover, ablation of FAP+ cells markedly enhanced endogenous T cell infiltration which further enhanced anti-tumor immunity and immunotherapy in PDAC models. Thus, our findings established that FAP-CAR T cell-mediated ablation of immunosuppressive FAP+-CAFs and disruption of the desmoplastic stroma they generate, can enhance accumulation and functionality of endogenous anti-tumor immunity and CAR-T cell therapy in the context of highly desmoplastic solid tumors. Citation Format: Zebin Xiao, Leslie A. Hopper, Meghan C. Kopp, Emily McMillan, Yue Li, Richard L Barrett, Ellen Puré. Disruption of tumor-promoting desmoplasia by adoptive transfer of fibroblast activation protein targeted chimeric antigen receptor (CAR) T cells enhances anti-tumor immunity and immunotherapy [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr C009.
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Chia, Jean-San, Chiou-Yueh Yeh, and Jen-Yang Chen. "Identification of a Fibronectin Binding Protein from Streptococcus mutans." Infection and Immunity 68, no. 4 (April 1, 2000): 1864–70. http://dx.doi.org/10.1128/iai.68.4.1864-1870.2000.
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ABSTRACT The interaction of viridans streptococci with components of the extracellular matrix (ECM) plays an important role in the pathogenesis of infective endocarditis. We have identified a surface protein ofStreptococcus mutans which binds the ECM constituent fibronectin (Fn). Initially, we found that S. mutans could adsorb soluble Fn in plasma, but with lower efficiency thanStreptococcus pyogenes. In addition, S. mutanscould bind immobilized Fn in a dose-dependent manner when tested using an enzyme-linked immunosorbent assay. Crude extracts of cell wall-associated proteins or extracellular proteins from S. mutans MT8148 specifically bound Fn through a protein with the molecular mass of ca. 130 kDa, as detected by far-Western immunoblotting. The candidate Fn binding protein (FBP-130) was purified to near homogeneity by using Fn coupled Sepharose 4B affinity column chromatography. A rabbit polyclonal antibody against FBP-130 reacted specifically with a protein of molecular mass of ca. 130 kDa in both cell wall and extracellular fractions, and the abundance of FBP was higher in the former than in the latter fractions. The purified FBP bound specifically to immobilized Fn, whereas the binding of soluble Fn to coated FBP could only be detected in the presence of high concentrations of Fn. The purified FBP, as well as anti-FBP immunoglobulin G, inhibited the adherence of S. mutans to immobilized Fn and endothelial cells (ECV304) in a dose-dependent manner. These results demonstrated that FBP-130 mediated the adherence of S. mutans specifically to Fn and endothelial cells in vitro. The characteristics of S. mutans and FBP-130 in binding Fn confirmed that viridans streptococci adopt different strategies in their interaction with ECM.
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Eieland, Alexander K., Kjersti R. Normann, Arvind Y. M. Sundaram, Tuula A. Nyman, Kristin A. B. Øystese, Tove Lekva, Jens P. Berg, Jens Bollerslev, and Nicoleta C. Olarescu. "Distinct Pattern of Endoplasmic Reticulum Protein Processing and Extracellular Matrix Proteins in Functioning and Silent Corticotroph Pituitary Adenomas." Cancers 12, no. 10 (October 14, 2020): 2980. http://dx.doi.org/10.3390/cancers12102980.
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Functioning (FCA) and silent corticotroph (SCA) pituitary adenomas act differently from a clinical perspective, despite both subtypes showing positive TBX19 (TPIT) and/or adrenocorticotropic hormone (ACTH) staining by immunohistochemistry. They are challenging to treat, the former due to functional ACTH production and consequently hypercortisolemia, and the latter due to invasive and recurrent behavior. Moreover, the molecular mechanisms behind their distinct behavior are not clear. We investigated global transcriptome and proteome changes in order to identify signaling pathways that can explain FCA and SCA differences (e.g., hormone production vs. aggressive growth). In the transcriptomic study, cluster analyses of differentially expressed genes revealed two distinct groups in accordance with clinical and histological classification. However, in the proteomic study, a greater degree of heterogeneity within the SCA group was found. Genes and proteins related to protein synthesis and vesicular transport were expressed by both adenoma groups, although different types and a distinct pattern of collagen/extracellular matrix proteins were presented by each group. Moreover, several genes related to endoplasmic reticulum protein processing were overexpressed in the FCA group. Together, our findings shed light on the different repertoires of activated signaling pathways in corticotroph adenomas, namely, the increased protein processing capacity of FCA and a specific pattern of adhesion molecules that may play a role in the aggressiveness of SCA.
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Cardoso, I., M. Brito, and M. J. Saraiva. "Extracellular Matrix Markers for Disease Progression and Follow-Up of Therapies in Familial Amyloid Polyneuropathy V30M TTR-Related." Disease Markers 25, no. 1 (2008): 37–47. http://dx.doi.org/10.1155/2008/549872.
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Familial Amyloidotic Polyneuropathy (FAP) is a disorder characterized by the extracellular deposition of fibrillar Transthyretin (TTR) amyloid, with a special involvement of the peripheral nerve. Several extracellular matrix proteins have been found elevated in tissues from FAP patients, namely metalloproteinase-9 (MMP-9), neutrophil gelatinase associated lipocalin (NGAL) and biglycan. In this work we assessed the levels of MMP-9, tissue inhibitor of metalloproteinase 1 (TIMP-1), NGAL, biglycan and chondroitin sulphate (CSPG) in an FAP V30M TTR-related transgenic mouse model at different stages of TTR deposition and after two different treatment approaches to remove fibrillar deposits. Immunohistochemistry or RT-PCR analysis showed that biglycan was already increased in animals presenting TTR deposited in a non-fibrillar state, whereas MMP-9, TIMP-1, NGAL and CSPG were elevated only in mice with TTR amyloid deposits. Mice treated with doxycycline, a TTR fibril disrupter, presented lower levels of MMP-9, TIMP-1 and NGAL, suggestive of matrix recovery. Mice immunized with TTR Y78F to remove TTR deposition showed significantly lower levels of all the five tested markers, suggesting removal of fibrillar and non-fibrillar deposits. Cellular studies using oligomeric TTR showed induction of MMP-9 when compared to soluble TTR, large aggregates or fibrils. Furthermore, this induction was neutralized by an anti-receptor for advanced glycation end products (RAGE) antibody, indicating RAGE engagement in this process. Further studies in a larger number of tissue samples will indicate the application of these ECM markers in parallel with Congo Red staining in tissue characterization of pre-clinical and clinical stages in FAP and other amyloidoses.
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Comba, Andrea, Syed M. Faisal, Maria Luisa Varela, Anna Argento, Patrick Dunn, Clifford Abel, Todd Hollon, et al. "TMIC-62. INHIBITION OF TUMOR-ASSOCIATED COL1A1 MATRIX ARRESTS GLIOMA MESENCHYMAL TRANSFORMATION AND REPROGRAMS THE TUMOR MICROENVIRONMENT." Neuro-Oncology 24, Supplement_7 (November 1, 2022): vii285. http://dx.doi.org/10.1093/neuonc/noac209.1106.
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Abstract Tumor mesenchymal transformation (MT) is a hallmark of high-grade gliomas. The mesenchymal state is associated with specific changes related to cell adhesion, migration, and the extracellular matrix. Collagen 1a1 (COL1A1) is a main component of the extracellular matrix in gliomas, and its expression correlates inversely with patient survival. However, the cellular and molecular mechanisms of the tumor-associated COL1A1 matrix in gliomas remains elusive. Our study integrates histopathological features, spatially resolved transcriptomics, cellular dynamics and microenvironment alterations associated with MT in high-grade gliomas. Using deep learning analysis of mouse and human glioma histological samples we identified that the density of areas of MT, named oncostreams, correlates with tumor aggressiveness. Spatial transcriptomics analysis, using laser capture microdissection, identified a signature enriched in extracellular matrix related proteins, in which COL1A1 appeared as a key determinant of mesenchymal organization. Correspondingly, human and mouse high-grade gliomas showed prominent alignment of collagen fibers along these mesenchymal fascicles and higher COL1A1 expression compared to low-grade gliomas. Moreover, RNA fluorescent multiplex assays identified at single cell level that different cells within glioma tumors contribute to COL1A1 expression, including neoplastic cells and perivascular non-neoplastic cells such as ACTA2+, CYR61+ and FAP+. Inhibition of COL1A1 using genetically engineered mouse models decreased areas of mesenchymal transformation and increased survival. COL1A1 downregulation impaired tumor cell proliferation and remodeled the tumor microenvironment by reducing CD68+ macrophages/microglia cells, CD31+ endothelial cells, ACTA2+, CYR61+ and FAP+ perivascular cells, and increased GFAP+ astrocytes infiltration withing the tumor mass. Further studies, using ex-vivo glioma explants demonstrated that CO1A1 downregulation decreased collective invasion of the normal brain, supporting its importance in tumor progression. We propose that COL1A1 expression is a valuable marker for diagnosis, and COL1A1 depletion within glioma tumors is a promising direct or complementary therapeutic approach to reprogram mesenchymal transformation, and halt tumor growth.
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Shi, Yixin, Ziren Kong, Penghao Liu, Guozhu Hou, Jiaming Wu, Wenbin Ma, Xin Cheng, and Yu Wang. "Oncogenesis, Microenvironment Modulation and Clinical Potentiality of FAP in Glioblastoma: Lessons Learned from Other Solid Tumors." Cells 10, no. 5 (May 10, 2021): 1142. http://dx.doi.org/10.3390/cells10051142.
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Currently, glioblastoma (GBM) is the most common malignant tumor of the central nervous system in adults. Fibroblast activation protein (FAP) is a member of the dipeptidyl peptidase family, which has catalytic activity and is engaged in protein recruitment and scaffolds. Recent studies have found that FAP expression in different types of cells within the GBM microenvironment is typically upregulated compared with that in lower grade glioma and is most pronounced in the mesenchymal subtype of GBM. As a marker of cancer-associated fibroblasts (CAFs) with tumorigenic activity, FAP has been proven to promote tumor growth and invasion via hydrolysis of molecules such as brevican in the extracellular matrix and targeting of downstream pathways and substrates, such as fibroblast growth factor 21 (FGF21). In addition, based on its ability to suppress antitumor immunity in GBM and induce temozolomide resistance, FAP may be a potential target for immunotherapy and reversing temozolomide resistance; however, current studies on therapies targeting FAP are still limited. In this review, we summarized recent progress in FAP expression profiling and the understanding of the biological function of FAP in GBM and raised the possibility of FAP as an imaging biomarker and therapeutic target.
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Dendl, Katharina, Stefan A. Koerber, Clemens Kratochwil, Jens Cardinale, Rebecca Finck, Mardjan Dabir, Emil Novruzov, et al. "FAP and FAPI-PET/CT in Malignant and Non-Malignant Diseases: A Perfect Symbiosis?" Cancers 13, no. 19 (September 30, 2021): 4946. http://dx.doi.org/10.3390/cancers13194946.
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A fibroblast activation protein (FAP) is an atypical type II transmembrane serine protease with both endopeptidase and post-proline dipeptidyl peptidase activity. FAP is overexpressed in cancer-associated fibroblasts (CAFs), which are found in most epithelial tumors. CAFs have been implicated in promoting tumor cell invasion, angiogenesis and growth and their presence correlates with a poor prognosis. However, FAP can generally be found during the remodeling of the extracellular matrix and therefore can be detected in wound healing and benign diseases. For instance, chronic inflammation, arthritis, fibrosis and ischemic heart tissue after a myocardial infarction are FAP-positive diseases. Therefore, quinoline-based FAP inhibitors (FAPIs) bind with a high affinity not only to tumors but also to a variety of benign pathologic processes. When these inhibitors are radiolabeled with positron emitting radioisotopes, they provide new diagnostic and prognostic tools as well as insights into the role of the microenvironment in a disease. In this respect, they deliver additional information beyond what is afforded by conventional FDG PET scans that typically report on glucose uptake. Thus, FAP ligands are considered to be highly promising novel tracers that offer a new diagnostic and theranostic potential in a variety of diseases.
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Xiao, Zebin, Leslie A. Hopper, Meghan C. Kopp, Emily McMillan, Yue Li, Richard L. Barrett, and Ellen Puré. "Abstract 2475: Visualization of cell to cell and cell to matrix interactions in the disruption of tumor-promoting desmoplasia by adoptive transfer of fibroblast activation protein targeted chimeric antigen receptor (CAR) T cells." Cancer Research 82, no. 12_Supplement (June 15, 2022): 2475. http://dx.doi.org/10.1158/1538-7445.am2022-2475.
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Abstract The efficacy of chimeric antigen receptor (CAR) T-cell therapy in solid tumors is limited by inefficient T-cell infiltration, localization and hypofunctionality within the tumor microenvironment. Prior studies demonstrated that stromal cell targeted CAR T cells, in particular CAR T cells that target fibroblast activation protein (FAP), can effectively infiltrate, and inhibit tumor growth in mouse models of pancreatic ductal adenocarcinomas (PDAC) due to their capacity to deplete stromal cells and extracellular matrix (ECM) that otherwise present a barrier to adoptive cell therapies. However, the kinetics of tumor infiltration by FAP-CAR T cells, and the cell-cell and cell-matrix interactions that contribute to their anti-tumor activity are poorly understood. A better understanding FAP-CAR T-cell kinetics and intratumoral interactions should provide insights into the requirements for successful adoptive cell therapies in solid tumors. By combining immunostaining and real-time two-photon microscopy in tumor fragments of PDAC, we found that stromal cell targeted FAP-CAR T cells can efficiently traffic into tumors. Initially (days 1-3) FAP-CAR T cells were enriched in the stroma surrounding tumor nests but excluded from the tumor nests per se. While associated with the stroma rich region, the CAR T cells appeared activated and T cell motility was observed in loose collagen regions, but T cells migrated poorly in dense matrix areas. Aligned collagen fibers in the tumor boarder dictated the migratory trajectory of T cells and restricted them from entering tumor nests. By day 5 we observed depletion of immunosuppressive stromal cells, dissolution of the fibrillar collagen network surrounding tumor nests and infiltration of FAP-CAR T cells into tumor nests. Treatment with hyaluronidase increased the ability of T cells to infiltrate the tumor nest. Thus, FAP-CAR T cell-mediated ablation of immunosuppressive FAP+ stromal cells and disruption of the desmoplastic stroma they generate, can enhance accumulation and functionality of CAR-T cell therapy in the context of highly desmoplastic solid tumors. Citation Format: Zebin Xiao, Leslie A. Hopper, Meghan C. Kopp, Emily McMillan, Yue Li, Richard L. Barrett, Ellen Puré. Visualization of cell to cell and cell to matrix interactions in the disruption of tumor-promoting desmoplasia by adoptive transfer of fibroblast activation protein targeted chimeric antigen receptor (CAR) T cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2475.
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Hoffmann, Daniel B., Daniela Fraccarollo, Paolo Galuppo, Stefan Frantz, Johann Bauersachs, and Jochen Tillmanns. "Genetic ablation of fibroblast activation protein alpha attenuates left ventricular dilation after myocardial infarction." PLOS ONE 16, no. 3 (March 5, 2021): e0248196. http://dx.doi.org/10.1371/journal.pone.0248196.
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Introduction Regulating excessive activation of fibroblasts may be a promising target to optimize extracellular matrix deposition and myocardial stiffness. Fibroblast activation protein alpha (FAP) is upregulated in activated fibroblasts after myocardial infarction (MI), and alters fibroblast migration in vitro. We hypothesized that FAP depletion may have a protective effect on left ventricular (LV) remodeling after MI. Materials and methods We used the model of chronic MI in homozygous FAP deficient mice (FAP-KO, n = 51) and wild type mice (WT, n = 55) to analyze wound healing by monocyte and myofibroblast infiltration. Heart function and remodeling was studied by echocardiography, morphometric analyses including capillary density and myocyte size, collagen content and in vivo cell-proliferation. In non-operated healthy mice up to 6 months of age, morphometric analyses and collagen content was assessed (WT n = 10, FAP-KO n = 19). Results Healthy FAP-deficient mice did not show changes in LV structure or differences in collagen content or cardiac morphology. Infarct size, survival and cardiac function were not different between FAP-KO and wildtype mice. FAP-KO animals showed less LV-dilation and a thicker scar, accompanied by a trend towards lower collagen content. Wound healing, assessed by infiltration with inflammatory cells and myofibroblasts were not different between groups. Conclusion We show that genetic ablation of FAP does not impair cardiac wound healing, and attenuates LV dilation after MI in mice. FAP seems dispensable for normal cardiac function and homeostasis.
Dissertations / Theses on the topic "Extracellular Matrix FCP"
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LOCATELLI, LUIGI. "Expression of aVB6 integrin by Pkhd1-defective cholangiocytes links enhanced ductal secretion of Macrophage chemokines to progressive portal fibrosis in Congenital Hepatic Fibrosis." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2013. http://hdl.handle.net/10281/41733.
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BACKGROUND AND AIMS: Congenital Hepatic Fibrosis (CHF) is caused by mutations in PKHD1, a gene encoding for fibrocystin, a protein of unknown function, expressed in cholangiocyte cilia and centromers. In CHF, biliary dysgenesis is accompanied by severe progressive portal fibrosis and portal hypertension. The mechanisms responsible for portal fibrosis in CHF are unclear. The αvβ6 integrin mediates local activation of TGFβ1 and is expressed by reactive cholangiocytes during cholestasis. To understand the mechanisms of fibrosis in CHF we studied the expression of αvβ6 integrin and its regulation in Pkhd1del4/del4 mice.
METHODS: In Pkhd1del4/del4 mice we studied, at different ages (1-12 months): a) portal fibrosis (Sirius Red) and portal hypertension (spleen weight/body weight); b) αvβ6 mRNA and protein expression (RT-PCR, IHC); c) α-SMA and TGFβ1 mRNA expression (RT-PCR); d) portal inflammatory infiltrate (IHC for CD45 and FACS analysis of whole liver infiltrate); f) cytokines secretion from cultured monolayers of primary cholangiocytes (Luminex assay); g) cytokine effects on monocyte/macrophage proliferation (MTS assay) and migration (Boyden chamber); h) TGFβ1 and TNFα effects on β6 integrin mRNA expression by cultured cholangiocytes before and after inhibition of the TGFβ receptor type II (TGFβRII); i) TGFβ1 effects on collagen type I (COLL1) mRNA expression by cultured cholangiocytes.
RESULTS: Pkhd1del4/del4 mice showed a progressive increase in αvβ6 integrin expression on biliary cyst epithelia. Expression of αvβ6 correlated with portal fibrosis (r=0.94, p<0.02) and with enrichment of a CD45+ve cell infiltrate in the portal space (r=0.97, p<0.01). Gene expression of TGFβ1 showed a similar age-dependent increase. FACS analysis showed that 50-75% of the CD45+ve cells were macrophages (CD45/CD11b/F4/80+ve). Cultured polarized Pkhd1del4/del4 cholangiocytes secreted from the basolateral side significantly increased amounts of CXCL1 and CXCL10 (p<0.05). Both cytokines were able to stimulate macrophage migration (p<0.05). Basal expression of β6 mRNA by cultured Pkhd1del4/del4 cholangiocytes (0.015±0.002 2^-dCt) was potently stimulated by the macrophage-derived cytokines TGFβ1 (0.017±0.002 2^-dCt, p<0.05) and TNFα (0.018±0.003 2^-dCt, p<0.05). Inhibition of TGFβRII completely blunted TGFβ1 (0.014±0.003 2^-dCt, p<0.05) but not TNFα effects (0.017±0.001 2^-dCt, p=ns) on β6 mRNA. COLL1 mRNA expression by cultured Pkhd1del4/del4 cholangiocytes (0.0009±0.0003 2^-dCt) was further and significantly increased after TGFβ1 stimulation (0.002±0.0005 2^-dCt, p<0.05).
CONCLUSIONS: Pkhd1del4/del4 cholangiocytes possess increased basolateral secretory functions of chemokines (CXCL1, CXCL10) able to orchestrate macrophage homing to the peribiliary microenvironment. In turn, by releasing TGFβ1 and TNFα, macrophages up-regulate αvβ6 integrin in Pkhd1del4/del4 cholangiocytes. αvβ6 integrin activates latent TGFβ1, further increasing the fibrogenic properties of cholangiocytes.
Conference papers on the topic "Extracellular Matrix FCP"
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Lu, Xin, Daniel D. Sun, X. Edward Guo, Hui Chen, W. Michael Lai, and Van C. Mow. "Use of Indentation Test to Determine the Proteoglycan Content of Articular Cartilage." In ASME 2002 International Mechanical Engineering Congress and Exposition. ASMEDC, 2002. http://dx.doi.org/10.1115/imece2002-32619.
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The indentation experiment has been widely used to determine mechanical properties of articular cartilage [e.g., 1–3]. This method does not disrupt the fibrous network of the tissue nor does it require removing the tissue from the underlying bone. The biphasic indentation theory has been successfully used to determine the effect of interstitial fluid flow and pressurization (load support) on the creep and stress-relaxation behaviors of articular cartilage, and to determine its apparent mechanical properties (i.e., the elastic moduli of the extracellular solid matrix and its permeability) [1, 3]. However, due to its proteoglycan content, articular cartilage is a charged tissue with a high fixed charge density (FCD) [4]. Proteoglycan and collagen contents, water, etc, vary with age or with orthteoarthritis [4, 5]. The FCD plays important physicochemical roles in load support and mechano-electrochemial behaviors of the tissue and also regulates chondrocyte biosynthetic activities [4–7]. It is therefore important to develop an effective technique to determine not only the mechanical properties but also the electrochemical property (e.g., FCD) of the tissue, simultaneously and at the same location. The purpose of the current study is to determine, for the first time, both the mechanical properties and FCD of the extracellular matrix using an indentation test.
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Jackson, Alicia R., Tai-Yi Yuan, Chun-Yuh Huang, and Wei Yong Gu. "A Two-Point Conductivity Approach to Measuring Fixed Charge Density in Intervertebral Disc Tissue." In ASME 2009 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2009. http://dx.doi.org/10.1115/sbc2009-206310.
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Low back pain, a major socio-economic concern in the United States, is believed to result from degeneration of the intervertebral disc (IVD) of the spine [1]. The IVD is characterized as a charged, hydrated soft tissue made up of a central nucleus pulposus (NP) surrounded by the layered annulus fibrosus (AF). The negatively-charged nature of the disc derives from the charged groups attached to the glycosaminoglycan (GAG) molecules found on proteoglycans (PG) in the extracellular matrix of the disc. The fixed charge density (FCD) is a measure of the number of negative charges attached to the disc matrix per unit volume. FCD is important to disc function, both mechanically (i.e., swelling pressure) and in terms of transport through the disc [2].
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Yoshida, Kyoko, Claire Reeves, MiJung Kim, Jan Kitajewski, Joy Vink, Ronald Wapner, David Paik, and Kristin Myers. "Cervical Collagen Network Remodeling in Normal and Disrupted Parturition Mouse Models." In ASME 2013 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/sbc2013-14508.
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The cervix plays an important role in pregnancy as a mechanical barrier to prevent preterm birth (PTB). The material strength of the cervix can be attributed to its extracellular matrix (ECM), a network of cross-linked collagens (types I and III) embedded within a viscous matrix of glycosaminoglycans (GAG). GAGs are negatively charged polysaccharides that provide a fixed charge density (FCD) within the tissue to maintain hydration. Throughout gestation, the ECM of the cervix undergoes a remodeling process characterized by three stages: gradual softening in early pregnancy, a rapid increase in tissue distensibility termed ripening in late pregnancy, and repair at post partum 1. As the cervix softens and ripens, mature collagen cross-links break down while GAG content increases 2,3. Previous research has shown that these changes in collagen and GAGs correlate to a mechanically softer cervix at term 4.
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Gao, Xin, Lingtu Meng, Chun-Yuh C. Huang, and Weiyong Gu. "Contributions of Proteoglycans to the Biotransport and Electrical Properties of Articular Cartilage: An Experimental Study." In ASME 2013 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/sbc2013-14645.
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Proteoglycans (PGs) are one of the major components in the extracellular matrix (ECM) of cartilage, and are negatively charged due to the charged groups attached to their backbone (i.e., fixed charge groups). PGs play substantial roles in the mechanical, biotransport and electrical events within the tissue.3,7 More specifically, swelling pressure generated by the interaction between fixed charge groups and ionic interstitial fluid enhances cartilage’s capacity of load-bearing. In addition, biotransport properties (e.g., hydraulic permeability) and electrical properties (e.g., electrical conductivity) have been shown to be affected by water content (i.e., porosity) and fixed charge density (FCD).2–4 The alteration of proteoglycan content will affect the tissue FCD and water content, which could cause the changes in biomechanical, biotransport and electrical properties of the cartilage. The relationship between the PG content and biomechanical properties has been widely studied,6,8 but the knowledge on the effects of PG content on biotransport and electrical properties is limited.1 It is not clear whether the dependences of biotransport and electrical properties on PG content are mainly due to electric effects through the FCD associated with PGs or due to hindrance effects related to the effective pore size (i.e., water content) of the tissue. Therefore, the objectives of this study were (1) to investigate the effects of PG content on cartilage biotransport and electrical properties, (2) to analyze whether these effects are caused by changes of water content or FCD.
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Yao, Hai, and Wei Yong Gu. "Analysis of Solute Transport in Cartilaginous Tissue Under Dynamic Unconfined Compression." In ASME 2003 International Mechanical Engineering Congress and Exposition. ASMEDC, 2003. http://dx.doi.org/10.1115/imece2003-43066.
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Transport of fluid and solutes through the extracellular matrix plays a key role in the nutrition and growth of cartilaginous tissues that lack blood supply. It has been found that the mechanical loading can alter the transport rates of solutes within cartilage [Bonassar, 2000; O’Hara, 1990; Quinn, 2002]. Dynamic compression may enhance the transport of large solutes (e.g., growth factors) within the tissue. Many theoretical analyses have been reported in literature on the transport of fluid and solutes, as well as physical signals (stress, strain, pressure, concentrations, and electrical potential) in cartilage under unconfined compression [Armstrong, 1984; Levenston, 1999; Mow, 2002]. However, little is known as to how the tissue fixed charge density (FCD) affects the transport of fluid and neutral solutes (e.g., glucose and IGF-1) in cartilage sample in dynamic compression. In this study, we numerically analyzed the transport of fluid and solutes, as well as the mechano-electrochemical signals within the cartilage sample in dynamic unconfined compression, using the finite element method (FEM). The objective of this study was to investigate the effects of FCD, loading frequency, and loading platens (permeable vs. impermeable) on the transport of fluid, ions, and neutral solutes within cartilage. This study is essential for the understanding of tissue nutrition and signal transduction mechanisms in cartilage subjected to mechanical forces.