Dissertationen zum Thema „Membrane, Basement“
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1
Cleutjens, Jacobus Peter Marie. „Basement membrane heterogeneity“. Maastricht : Maastricht : Rijksuniversiteit Limburg ; University Library, Maastricht University [Host], 1989. http://arno.unimaas.nl/show.cgi?fid=5472.
2
Wootton, Andrew. „The glomerular basement membrane and nephritis /“. Title page, contents and abstract only, 1985. http://web4.library.adelaide.edu.au/theses/09PH/09phw918.pdf.
3
Devaka, K. Weerakoon Cheung H. Tak. „Interaction of macrophages with the basement membrane“. Normal, Ill. Illinois State University, 1995. http://wwwlib.umi.com/cr/ilstu/fullcit?p9603526.
Annotation:
Thesis (Ph. D.)--Illinois State University, 1995.Title from title page screen, viewed May 8, 2006. Dissertation Committee: Hou Tak Cheung (chair), David W. Borst, Herman E. Brockman, Alan J. Katz, Anthony J. Otsuka. Includes bibliographical references (leaves 98-110) and abstract. Also available in print.
4
Visser, Robbert. „Basement membrane antigens in preneoplastic and neoplastic conditions“. Maastricht : Maastricht : Universitaire Pers Maastricht ; University Library, Maastricht University [Host], 1993. http://arno.unimaas.nl/show.cgi?fid=5867.
5
Melian, Nadia. „Basement membrane composition of Dag1 null chimaeric mice kidneys“. Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=33809.
Annotation:
The growth of an organism involves the proliferation and migration of cells within an extracellular matrix. As a cell surface receptor, the Dag1 gene product dystroglycan links the intracellular cytoskeleton to the extracellular basement membrane in many cells. Thought to act as a structural protein dystroglycan may also participate in signal transduction. This study aims to better understand the role of dystroglycan during kidney morphogenesis. I hypothesised that a lack of dystroglycan in the precursor cells of the kidney could lead to altered kidney growth. Chimaeric mice deficient in dystroglycan were generated to test this hypothesis. A total of 38 chimaeras had genetic contribution and histological analysis performed on their kidneys. Of the chimaeras analysed, only four demonstrated altered kidney morphology. Further histological, immunohistochemical and biochemical studies established whether a link existed between this morphology and a deficiency in dystroglycan. Normal laminar architecture and nephrotic structures of the kidneys suggest that normal kidney organogenesis occurred in the absence of dystroglycan. The pattern and expression level of basement membrane components suggests that normal basement membrane formation also occured in the absence of dystroglycan. Biochemical analysis revealed that although dystroglycan protein levels correlate with the genetic contribution of the chimaeric kidney, it does not correlate with the altered morphology. Ureter blockage causing hydronephrosis can explain the morphology observed. A deficiency of dystroglycan in the ureter may in turn have caused this blockage. These findings suggest that dystroglycan is not necessary for kidney organogenesis, since kidney development occurred normally in all 38 chimaeric animals irrespective of genetic contribution.
6
Burton, Victoria Jane. „Neutrophil migration through endothelial cells and their basement membrane“. Thesis, University of Birmingham, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.532273.
7
Forster, Simon J. „Basement membrane proteins and the spread of rectal cancer“. Thesis, University of Leicester, 1987. http://hdl.handle.net/2381/35223.
Annotation:
Antisera to the basement membrane proteins laminin, fibronectin and type IV collagen were prepared, characterized and rendered monospecific by appropriate treatments. Methods were developed to allow the use of these antisera for inmunohistochemical staining of sections of tissue which had been preserved by several methods. In particular, the use of protease digestion {"unmasking") to allow staining of formalin-fixed, paraffin-embedded material was studied. The presence and intensity of staining was found to be highly dependent on the protease and the conditions of digestion, the type of basement membrane, and whether the tissue was normal or neoplastic. The distributions of the three proteins were studied in normal colorectal mucosa and in colorectal adenocarcinoma. A detailed retrospective study was made of the distribution of laminin in 158 cases of rectal carcinoma. Tumours fell into two groups: those which showed linear basement membrane-like laminin staining (laminin positive) and those which did not (laminin negative). Patients with laminin positive tumours had a reduced incidence of distant metastasis and an increased 5 yr survival rate; these correlations were statistically highly significant. Carparison by multivariate analysis with other widely used prognostic markers indicated that laminin status has considerable potential for use as a prognostic marker in the management of such patients. The antisera were also used in a study of the cellular origin and biosynthesis of basement membrane proteins in three systems. In a basement membrane-producing murine tumour, intracellular staining was seen, but it was found that different methods of tissue preparation and unmasking drastically affected the apparent distributions of the three antigens. In the developing rat intestine, no evidence was seen of basement membrane synthesis by the intestinal epithelial cells. However in isolated rat intestinal epithelial cells, some evidence was found for synthesis of laminin and fibronectin, but not type IV collagen.
8
Garton, Rosemary Louise. „The influence of basement membrane proteins on re-vascularization networks formed after acute injury“. Thesis, The University of Sydney, 1997. http://hdl.handle.net/2123/4817.
9
Zhang, Xu. „Basal lamina genes affected in leiomyomatosis and congenital muscular dystrophy : structure and mutation analyses of the collagen COL4A6 and laminin LAMA2 genes“. Stockholm, 1997. http://diss.kib.ki.se/1997/91-628-2780-4.
10
Li, Yi-Yang Cheung H. Tak. „Basement membrane and its components on lymphocyte adhesion, migration, and proliferation“. Normal, Ill. Illinois State University, 1992. http://wwwlib.umi.com/cr/ilstu/fullcit?p9234466.
Annotation:
Thesis (Ph. D.)--Illinois State University, 1992.Title from title page screen, viewed January 27, 2006. Dissertation Committee: H. Tak Cheung (chair), Anthony Otsuka, Alan Katz, Brian Wilkinson, David Weber. Includes bibliographical references (leaves 108-120) and abstract. Also available in print.
11
Shima, Thomas Brent. „Isolation, structural and immunohistochemical characterization of basement membrane heparan sulfate proteoglycan“. Thesis, McGill University, 1992. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=61197.
Annotation:
Heparan sulfate proteoglycan (HSPG) was isolated from the mouse Engelbreth-Holm-Swarm (EHS) tumor. Polyclonal antibodies against the isolated HSPG were raised by two separate techniques, both producing highly reactive antisera. The antisera were found to be reactive against epithelial basement membrane of the mouse foot pad, glomerular basement membrane of the kidney and the EHS tumor matrix using the techniques of light microscopic immunoperoxidase on frozen sections and electron microscopic immunogold labelling on ultrathin Lowicryl K4M sections. At high magnification of the EHS tumor matrix, the gold particles were found over 5 nm wide sets of parallel lines, referred to as "double tracks" (Inoue et al., 1989). When HSPG was incubated in 50 mM Tris buffer, pH 7.4, at 35$ sp circ$C for either 5 min or 1 hr, a precipitate resulted which was made up of 5-6 nm wide sets of parallel lines, similar to double track structures. Together these studies demonstrate that HSPG of the EHS tumor matrix is made up of double track structures, and that in vitro incubation of HSPG produces double track structures in as short a time as 5 min.
12
Tein, Mark S. C. „Studies on basement membrane permeation : models of pathogenic mechanims of glomerulonephritis“. Thesis, University of Oxford, 1994. http://ora.ox.ac.uk/objects/uuid:22440bfc-e712-4f7c-a11d-2eed9b07bcb6.
Annotation:
The effects of the biological cross-linker transglutaminase, the neutrophil oxidant hydrogen peroxide, and neutrophil proteinases on glomerular basement membrane permeability have been examined using an in vitro model of glomerular ultrafiltration. The main focus of the study lies in determining whether any of the test agents were able to render glomerular basement membrane more permeable to protein. Guinea pig liver transglutaminase was used as a model enzyme to test for the effect of biological cross-linkers on glomerular basement membrane permeability. It cross-linked glomerular basement membrane proteins, caused membrane contraction, and rendered glomerular basement membrane less permeable both to water and the low molecular weight protein marker myoglobin but had no effect on the membrane permeability to the high molecular weight marker protein bovine serum albumin or serum protein. The pathophysiological relevance of the effect is discussed. Hydrogen peroxide increased glomerular basement membrane permeability to water and proteins but the effect depended on hydrogen peroxide concentration and incubation time. The minimum concentration needed to render glomerular basement membrane more permeable to bovine serum albumin and serum protein was 1 M and the minimum incubation time needed was 6 hrs. A respiratory burst analysis of activated neutrophils showed that the average concentration of hydrogen peroxide that could be generated by the neutrophils was less than 50 mM and the time taken for extracellular hydrogen peroxide concentration to fall off to zero was less than 1 hr. Therefore, neutrophils seemed unable to generate and sustain a sufficiently high hydrogen peroxide concentration to render glomerular basement membrane more permeable to protein in vivo. Proteinases extracted from pig neutrophil granules were used to assess their effect on glomerular basement membrane permeability. The extract showed activity against glomerular basement membrane and the activity was primarily attributed to the serine proteinases elastase and cathepsin G, judged from substrate and inhibitor analyses. The proteinase extract also contain latent metalloproteinases, activatable by the organomercurial 4-aminophenyl mercuric acetate and calcium ions. Once activated, they also showed activity against glomerular basement membrane. The extract rendered glomerular basement membrane more permeable to water, myoglobin, bovine serum albumin, and serum protein. The increase in membrane permeability to water and proteins was due to membrane thinning and an increase in the intrinsic porosity of the membrane. When the serine and metalloproteinases were allowed to act in concert, they synergistically degraded glomerular basement membrane and increased the membrane permeability to serum protein and water. The study provides the first direct evidence that pathophysiological amounts of serine and metalloproteinases are able to render glomerular basement membrane more permeable to protein and suggests they may be capable of promoting proteinuria in neutrophil-dependent forms of immune glomerulonephritis.
13
Levy, Somin Gabriel. „The iridocorneal-endothelial syndrome : a study of cell and basement membrane pathology“. Thesis, University College London (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.309311.
14
Pereira, Inês Tavares Pinto de Sá. „Basement membrane alterarions in kernicteric brain microvasculature and pericyte response to bilirubin“. Master's thesis, FCT-UNL, 2011. http://hdl.handle.net/10362/6771.
Annotation:
Dissertação para obtenção do Grau de Mestre em
Genética Molecular e BiomedicinaKernicterus is a neuropathological condition characterized by deposition of unconjugated bilirubin (UCB) in specific brain regions that can lead to permanent sequelae and death, particularly in premature infants. UCB-induced toxicity has been studied in nerve and glial cells and, more recently, in brain microvascular endothelial cells. However, the effects of UCB on pericytes or on the basement membrane were never reported. We performed in vitro studies to assess apoptotic death, nitrosative stress and inflammatory reaction elicited by human brain vascular pericytes exposed to UCB. We also assessed the basement membrane component, collagen type IV, in brain sections of cortex, basal nuclei,hippocampus and cerebellum, collected at autopsy of a kernicteric preterm newborn. Using the pericyte marker, α-smooth muscle actin, we characterized the cells and confirmed the normal outgrowth towards a typical morphology with long processes. UCB induced an early secretion of interleukin-6, followed by that of vascular endothelial growth factor. mRNA upregulation preceded the secretion and confirmed the precocious profile of IL-6. UCB also caused the release of nitrites, which was maximum at 72 h incubation. The earlier upregulation of endothelial nitric oxide synthase expression confirmed the induction of nitric oxide production by UCB, although not excluding that other isoforms of the enzyme are also involved. Probably as a corolary of all these events, apoptotic cell death occurs in a time- and concentration-dependent manner. Through immunohistochemistry we examined the area occupied and the immunoreactivity of collagen type IV, which were reduced in the kernicterus case as compared with a non-icteric control. These findings are the first to demonstrate the compromise of pericytes and the impairment of collagen IV by hyperbilirubinemia and raise some basis for creation of possible target-directed therapy against pericyte and basement membrane damages as a result of UCB exposure.
15
Wheatcroft, Alison Clare. „Detection of type IV collagen degradation in inflammatory bowel disease“. Thesis, University of Sheffield, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.310765.
16
Walton, H. A. „The effect of structural modifications on the permeation properties of renal basement membrane“. Thesis, University of Oxford, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.382711.
17
McGrath, John Alexander. „Abnormalities of wound healing and basement membrane zone composition in dystrophic epidermolysis bullosa“. Thesis, King's College London (University of London), 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.343791.
18
Fields, Christopher J. „Functional and Expression Analysis of a Novel Basement Membrane Degrader in Drosophila Melanogaster“. TopSCHOLAR®, 2016. http://digitalcommons.wku.edu/theses/1633.
Annotation:
The Srivastava Lab is focused on the identification and characterization of genes that play a role in basement membrane remodeling. Previously, we identified putative basement membrane degraders through a genetic screen. One such gene has been suggested to play a role in the maintenance of the stem cell niche in Drosophila melanogaster, but no other information about the role this gene plays in development or disease has been published. Here, data are presented from experiments utilizing Drosophila genetics and immunohistochemistry that provide important insights on the biological role of this gene.
Collagenase activity was up-regulated upon overexpression of this gene, confirming it as a basement membrane degrader. Additionally, RNA in-situ hybridization experiment results showed expression in the developing imaginal discs of the 3rd instar larva tissues. Overexpression and knockdown studies further demonstrated morphological defects in a number of tissues, including the wing and the eye, and are suggestive of apoptosis. Acridine orange staining confirmed that cell death occurred when the gene was overexpressed and a cleaved caspase antibody staining indicated that process to be caspase-mediated apoptosis.
19
Falcone, Sara. „Nephrotic syndrome and glomerular basement membrane : genetic defect of the laminin α5 chain“. Thesis, Open University, 2018. http://oro.open.ac.uk/56060/.
Annotation:
Nephrotic syndrome is a heterogeneous group of disorders characterised by renal and extra-renal manifestations. Classic symptoms of nephrotic syndrome include severe proteinuria, hypoalbumiaemia, oedema and hyperlipidaemia. Genetic studies of hereditary forms of nephrotic syndrome have led to the identification of proteins playing a crucial role in slit diaphragm signalling, regulation of actin cytoskeleton dynamics and cell-matrix interactions. The laminin α5 chain is a 404 kDa protein essential for embryonic development and, in association with laminin β2 and laminin γ1, it is a major component of the glomerular basement membrane. Mutations in LAMB2 are associated with Pierson’s syndrome and mutations in LAMA5 have recently been identified in paediatric patients affected by nephrotic syndrome. As part of the MRC Harwell Ageing Screen, a large-scale ENU mutagenesis screen, a novel missense mutation (E884G) was identified in the gene Lama5. Homozygous mice showed a nephrotic phenotype including a severe proteinuria that preceded histological and ultrastructural changes. Further investigation using in vitro studies, extensive proteomics analysis and investigation of integrin activation, revealed a possible impact of the causative mutation on protein folding. Data suggest that changes in protein structure lead to a reduced secretion, integrin β1 activation, and agrin expression ultimately resulting in possible instability of the podocyte actin cytoskeleton.
20
Aypek, Hande [Verfasser]. „Loss of P3h2 gene causes thin basement membrane nephropathy in mice / Hande Aypek“. Hamburg : Staats- und Universitätsbibliothek Hamburg Carl von Ossietzky, 2020. http://d-nb.info/124083554X/34.
21
Martin, P. (Paula). „Type IV collagen:characterization of the COL4A5 gene, mutations in Alport syndrome, and autoantibodies in Alport and Goodpasture syndromes“. Doctoral thesis, University of Oulu, 2000. http://urn.fi/urn:isbn:9514256867.
Annotation:
Abstract
Type IV collagen is only found in basement membranes, where
it is the major structural component, providing a framework for
the binding of other basement membrane components and a substratum for
cells. The type IV collagen molecule is triple-helical and composed
of three a chains which exist as six distinct forms (α1 - α6).
Abnormalities in this basement membrane collagen structure and function
are connected to both inherited and acquired diseases.
Alport syndrome is a hereditary kidney disease associated
with extrarenal complications, such as sensorineural deafness and
eye abnormalities. The disease is caused by mutations in the COL4A3, COL4A4
and COL4A5 genes, coding for the type IV collagen α3, α4
and α5 chain genes, respectively. About 85% of
the Alport syndrome cases are X-linked dominant, caused by mutations in
the COL4A5 gene. In order to develop a basis for automated mutation
analysis of the COL4A5 gene, previously unknown intron sequences
flanking exons 2 and 37 were determined. Intron sequences flanking
the other 49 exons were expanded from 35 to 190, and additionally,
two novel 9 bp exons (exons 41A and 41B) were characterized in the
large intron 41. In addition to optimization of the PCR amplification
and sequencing conditions for all 51 exons and exon flanking sequences, optimization
for the 820 bp promoter region and for the two novel exons was performed
as well. Mutations were found in 79 unrelated patients of the 107
studied. This gives a high mutation detection rate of almost 75% in
comparison with 50%, at its best, in other extensive mutation
analyses of the COL4A5 gene using SSCP analysis. None of the mutations
involved the promoter region or exons 41A and 41B.
Circulating antibodies against basement membrane components
have been recognized in some autoimmune diseases. Goodpasture syndrome
is a rare autoimmune disease characterized by progressive glomerulonephritis
and pulmonary hemorrhage. The target of the antibodies in this disease
has been shown to be the noncollagenous NC1 domain of type IV collagen α3
chain. For unknown reasons, a minority of Alport syndrome patients
also develops antibodies against α3 and α5 chains
after renal transplantation with manifestation of severe anti-GBM
disease. In order to investigate the antibodies both in Goodpasture
and Alport syndrome, the NC1 domains of all six type IV collagen
chains were produced as recombinant proteins in bacterial and mammalian
expression systems, and an ELISA method was developed for antibody
detection. Antibodies were found in both syndromes, interestingly
also in Alport syndrome patients without the anti-GBM disease.
The results of this work have a significant clinical value
by providing for the first time complete, effective DNA-based analysis
of all exon/intron and promoter regions of the COL4A5 gene
in Alport syndrome.
22
McKenna, Declan Joseph. „Studies of the 67 kilodalton laminin receptor in retinal vasculature“. Thesis, Queen's University Belfast, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.300777.
23
Ali, Layla. „The structure and organization of type IV collagen in normal and glycated basement membrane“. Thesis, University of Exeter, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.413294.
24
Murray, Iain Colquhoun. „The immunohistochemical localization of basement membrane components to secretory organelles is observed in the youngest endothelial cells of the rat incisor, suggesting that the synthesis of basement membrane components occurs mainly in young cells“. Thesis, McGill University, 1986. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=65989.
25
Frith, P. A. F. „A study of eye involvement in autoimmune and inherited disorders of the basement membrane zone“. Thesis, University of Cambridge, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.599235.
26
Tang, Hailin. „Tissue specificity of a baculovirus-expressed, basement membrane-degrading protease in larvae of Heliothis virescens“. [Ames, Iowa : Iowa State University], 2008.
27
Salo, S. (Sirpa). „Laminin-5:function of the γ2 chain in epithelial cell adhesion and migration, and expression in epithelial cells and carcinomas“. Doctoral thesis, University of Oulu, 1999. http://urn.fi/urn:isbn:9514253426.
Annotation:
Abstract
Laminins are basement membrane glycoproteins consisting of
three polypeptide chains α, β and γ.
Until now 12 members of the protein family have been characterized
and all isoforms have an αβγ chain composition,
but they assemble in varying combinations of chain variants. The
functional properties of laminins include cell adhesion, proliferation,
differentiation, growth and migration. Laminin-5 has a chain composition
of α3β3γ2 with the distribution mainly
restricted to epithelial basement membranes, where its biological
functions involve anchorage and locomotion of cells. The importance
of this protein for the attachment of basal keratinocytes is clearly
demonstrated by the fact that all genes encoding its chains have
been shown to be mutated in the severe skin blistering disease
Epidermolysis bullosa junctionalis.
The present study focused on investigations of the role of
the laminin-5 isoform and particularly its γ2 chain in
cell adhesion and migration. The role of the short arm of the laminin γ2
chain in the process of epithelial cell attachment is to serve
as a kind of a bridging molecule to the extracellular environment,
because it does not have any cell binding activity by itself. It
was also shown that the newly synthesized γ2 chain participates
in the complex process of cell migration, probably as one of the
first attachment components for moving cells. Thus, as a migration
and differentiation-associated molecule, laminin-5 was considered
a potential marker for detection of malignant processes where cell
movement plays a role. Subsequently it was shown that the γ2
chain is expressed not only in a restricted manner in human epithelial
tissues, but also in a number of human epithelium-derived cancers.
In some carcinomas, expression of the γ2 chain appeared
to be a characteristic of cancer cells with invasive properties.
Examination of over 50 dysplasias and cervical tumors revealed
that γ2 chain antibodies were able to distinguish between
lesions with or without invasive capacity. This is the first systematic
study of epithelial cancers where γ2 chain antibodies
have been shown to be a useful marker in the histopathological
diagnostics. In addition, this study showed in a mouse tumor model
that the γ2 chain of laminin-5 has a potential for being
of use for in vivo tumor imaging.
28
Feru, Jezabel. „Etude de la diminution du collagène IV au cours du vieillissement cutané et des mécanismes impliqués“. Thesis, Reims, 2013. http://www.theses.fr/2013REIMS006/document.
Annotation:
Le vieillissement cutané s'accompagne d'altérations des composants de la matrice extracellulaire. Des études ont montré que le contenu en collagène IV diminuait dans la peau à partir de 35 ans. Le collagène IV, constituant majeur des membranes basales, est formé de l'association, en triple hélice, de 3 chaînes alpha parmi 6 possibles: alpha1(IV) à alpha6(IV). Au niveau de la membrane basale cutanée, encore appelée jonction dermo-épidermique, seulement deux isoformes de collagène IV ont été mises en évidence : [alpha1(IV)2; alpha2(IV)], isoforme majoritaire, et [alpha5(IV)2; alpha6(IV)], isoforme minoritaire, synthétisées par les fibroblastes et les kératinocytes. Nous avons vérifié, par western-blot sur des extraits de peaux, cette diminution de collagène IV. Nous avons ensuite analysé la répartition du collagène IV au niveau de la JDE sur des coupes transversales de peau et n'avons pu mettre en évidence de discontinuité dans le réseau de collagène IV avec l'âge, du fait des fortes variations inter-individuelles. Parallèlement, sur coupe de peau, nous avons tenté de mettre en évidence des différences spectrales du collagène IV avec l'âge par spectroscopie Raman mais la résolution s'est avérée insuffisante. Nous avons isolé des fibroblastes de patients d'âges différents et montré une diminution de l'expression génique de la chaîne alpha1(IV) malgré de fortes variations inter-individuelles. Afin de s'affranchir de ces variations inter-individuelles pour étudier les mécanismes impliqués dans la diminution d'expression du collagène IV, nous avons mis au point un modèle de vieillissement accéléré de fibroblastes traités à l'H2O2 et vérifié le phénotype sénescent des cellules (morphologie modifiée, augmentation de l'activité SA-beta-galactosidase, augmentation de p21WAF-1…). Nous nous sommes intéressé à la voie du TGF-beta1. Nous avons montré que l'expression du récepteur au TGF-beta1, TbetaRII, diminuait dans le modèle de vieillissement accéléré. Nous avons également montré qu'un anticorps bloquant anti-TGF-beta1 reproduisait la diminution d'expression de collagène IV observée au cours de la sénescence. La détermination du mécanisme impliqué pourrait permettre, à terme, de proposer de nouvelles stratégies pour maintenir l'intégrité de la membrane basale lors du vieillissement cutanéDuring aging skin there are extracellular matrix alterations. Preliminary studies showed that type IV collagen content decreased in skin with age after 35 years. Type IV collagen is a major component of basement membranes. It's constituted by the association of 3 alpha chains among 6 possible (alpha1 to alpha6). In the cutaneous basement membrane also called dermo-epidermal junction, only two isoform of type IV collagen were found: [alpha1(IV)2; alpha2(IV)], which is majoritary isoform, and [alpha5(IV)2; alpha6(IV)], which is minoritary, both synthesized by fibroblasts and keratinocytes. We checked the decrease in type IV collagen by western-blot on skin extracts. We then analyzed the distribution of this collagen in the DEJ on skin sections but we were not able to highlight a discontinuity in the network of type IV collagen during aging. At the same time, we tried to highlight spectral differences of the collagen IV with aging by Raman spectroscopy on skin sections but the resolution was insufficient. 35 years. We showed a decrease of type IV collagen expression by dermal fibroblasts in spite of strong variation between patients. In order to study the mechanism involved in type IV collagen variation during aging in dermal fibroblasts avoiding inter-individual variations, we develop an accelerated aging model of fibroblasts by treatment with H2O2. We checked the senescent phenotype of the cells (modified morphology, increase of SA-beta-galactosidase activity, increase of p21WAF-1…). We were interested on the TGF-1 pathway and we showed that TGF-beta1 receptor, called TbetaRII, was decreased in our accelerated aging model. We also showed that a blocking antibody against TGF-beta1 reproduced the decrease of type IV collagen expression observed during the senescence. The determination of the involved mechanism could lead to propose new strategies to maintain the integrity of the basal membrane during skin aging
29
Vatansever, Hafize Seda. „Analysis of basement membrane regulation and deposition during early mouse development in vivo and in vitro“. Thesis, University of Liverpool, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.364209.
30
Bolton, Glen R. (Glen Reed) 1970. „Permeation of ficoll and ficoll sulfate through glomeruler basement membrane : effects of molecular size and charge“. Thesis, Massachusetts Institute of Technology, 1998. http://hdl.handle.net/1721.1/50390.
31
Flinchum, Dane Alan. „Characterizing the Role of CP1 in Drosophila Melanogaster: Its Effects on Basement Membrane Degradation and Signaling“. TopSCHOLAR®, 2018. https://digitalcommons.wku.edu/theses/2642.
Annotation:
CP1 is a well-conserved cathepsin L-like protease essential for proper growth and development in Drosophila melanogaster. Previous research has demonstrated that CP1 has the ability to break down the extracellular matrix. Using the UAS-GAL4 system, immunohistochemistry, and antibody-staining, this research attempts to characterize the role of CP1 and its effects on basement membrane degradation and signaling. These effects include actions at the cellular level and on a known signaling pathway. The genes involved in this pathway are known to be required for proper development of the wing disc into the adult wing. We have demonstrated the collagenase activity of CP1 as well as a possible mechanism via TIMP. We have shown that cp1 is part of the wingless signaling pathway and potentially acts as an upstream regulator on wingless and nubbin. Finally, we have successfully inserted the cDNA of a potential inhibitor of CP1, titled crammer, into the vector pUAST to create transgenic flies.
Understanding how CP1 affects Drosophila development through cellular and gene activity is important because cathepsins are highly conserved between flies, humans, and have been implicated in several diseases, including cancer. Discovering the mechanisms by which CP1 functions allows for discoveries to be made in connection with disease processes.
32
Elamaa, H. (Harri). „Type XVIII collagen:characterization of the primary structure and expression pattern of different variants in Xenopus laevis, characterization of the human gene structure and analysis of transgenic mice expressing endostatin“. Doctoral thesis, University of Oulu, 2004. http://urn.fi/urn:isbn:9514275691.
Annotation:
Abstract
In this work the type XVIII collagen has been studied by using several approaches, such as different animal models. The primary structure of frog, Xenopus laevis, type XVIII collagen and the expression pattern of its variants during early embryogenesis have been elucidated. The gene structure of human type XVIII collagen was characterized and the localization and processing of its longest variant was studied by generated antibodies. In addition, the function of the proteolytically released C-terminal part of type XVIII collagen, endostatin, was studied by generating transgenic mice expressing endostatin.
The primary structure of X. laevis type XVIII collagen is comprised of three N-terminal variants resembling their mammalian counterparts. The sizes of the polypeptides are 1285, 1581, and 1886 residues. The most conserved regions are the C-terminal endostatin region and the cysteine-rich domain in the N-terminus. Whole-mount in situ hybridization reveals different expression patterns for variants during embryogenesis. The short variant is the most abundant, whereas the two longest variants exhibit more restricted expression.
The gene structure of human type XVIII collagen reveals an exon-intron organization that is conserved with mouse. The length of the human gene is about 105 kb and contains 43 exons. The third variant of type XVIII collagen has a conserved cysteine-rich domain with homology to the extracellular part of frizzled proteins. This third variant is localized to developing muscle and lung, and is also found in serum. In cell culture, the proteolytic fragments of the N-terminus, including the cysteine-rich motif, are also detected.
Endostatin function was studied by generating mouse lines expressing endostatin under the keratin-14 promoter, which drives the expression mainly in the skin. Three independent transgenic mouse lines were achieved with varied expression levels. The phenotype was seen in the eye with lens opacity and abnormal morphology of epithelial cells in the lens. In the skin, a broading of the basement membrane in the epidermis dermis junction was detected. Immunoelectron microscopy analysis revealed a polarized orientation of type XVIII collagen in the basement membrane. In transgenic mice, altered localization of endogenous type XVIII collagen was seen, suggesting displacement of the endogenous type XVIII collagen with transgenic endostatin leading to disorganized basement membrane.
33
Bevacqua, Sandra Jean. „An in vitro study of human melanoma tumor cell metastasis: Cytological and molecular events during extravasation“. Diss., The University of Arizona, 1989. http://hdl.handle.net/10150/184746.
Annotation:
In order to study the process by which human melanoma cells achieve invasion of basement membranes, a modification of the Membrane Invasion Culture System was developed to allow the in vitro collection of invasive tumor cells from heterogeneous tumor cell populations. A significant increase in the number of double minute chromosomes was observed in metaphase nuclei of the low metastatic A375P human melanoma cells which had invaded 2 consecutive amniotic membranes over that of cells in the control groups. After 25 days in culture, the incidence of double minutes had dropped below the control range. These data indicate that an unstable gene amplification event may be part of the process by which melanoma cells execute invasion through basement membranes. A375P cells which had invaded 1, 3 and 5 consecutive basement membrane-coated filters were established and compared with the parental cell line and a highly metastatic subclonal line for the following characteristics: (a) in vitro invasive potential, (b) mRNA expression of several oncogenes, (c) expression of laminin receptor, at the (cell surface) protein and mRNA levels, and, (d) secretion of endogenous laminin. There was a progressive increase in invasive potential and expression of endogenous laminin and laminin receptor which correlated with the number of membrane-coated filters through which the A375P cells had been selected. There were significant increases in the steady-state mRNA expression of c-myc and c-fos, a decrease in c-jun, and no change in Ha-ras, that correlated with increases in the invasive and metastatic potential of the cells. A novel in vitro adhesion assay was developed to study the interaction of tumor cells with lymphatic endothelium, the first step of extravasation from the lymphatic vessel. Human tumor cells from: one primary Ewing sarcoma, two melanoma, two colon and two breast carcinomas were assayed for their ability to attach to monolayers of lymphatic endothelium. There was a clear positive correlation between the metastatic potential and attachment potential of the melanoma cell lines. Overall, these data suggested that highly fibroblastic established tumor cell lines were more adaptive in rapid adhesion than primary tumor cell cultures with a more rounded morphology.
34
Lummerstorfer, Judith-Antonia. „The significance of the laminin-nidogen-1-interaction for basement membrane formation and stability in embryoid bodies“. [S.l. : s.n.], 2001. http://deposit.ddb.de/cgi-bin/dokserv?idn=962023485.
35
Öhlund, Daniel. „Basement membrane collagens in pancreatic cancer : novel stroma-derived tumor markers and regulators of cancer cell growth“. Doctoral thesis, Umeå universitet, Kirurgi, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-37555.
Annotation:
Background: Among the common malignancies, pancreatic cancer has the shortest long-term survival. The aggressive, rapid, and infiltrative growth pattern of pancreatic cancer, together with the lack of specific symptoms, often leads to late diagnosis. Metastases are frequently found at the time of diagnosis, which prevents curative surgical treatment. Good tumor markers would enable early detection, thus improving the prognosis. Unfortunately, no such markers are available in the clinic. The tumor stroma is defined as the non-malignant cells and the extracellular matrix (ECM) of a cancer. Pancreatic cancer is characterized by an abundant tumor stroma, rich in ECM proteins such as collagens, which have been shown to play important roles in tumor progression. Furthermore, pancreatic cancer cells produce large quantities of ECM proteins, especially the basement membrane (BM) protein type IV collagen. All epithelial cells are anchored to a BM, which must be degraded in order for an in situ cancer to become invasive. Matrix metalloproteinases (MMPs) are enzymes involved in BM degradation. In this thesis, the tumor stroma of pancreatic cancer is studied, focusing on the BM proteins type IV and type XVIII collagen, with the aim to clarify if the stroma could be a source of novel tumor markers for this form of cancer. Additionally, the role of type IV collagen produced by the cancer cells is studied. Methods: Expression patterns of type IV and type XVIII collagen, MMPs involved in collagen degradation, and collagen receptors (integrins) were studied by immunoflourescence in both normal and pancreatic cancer tissue, and in pancreatic cancer cell lines. Circulating plasma levels of type IV and type XVIII collagen and conventional tumor markers (TPS, Ca 19-9, CEA and Ca 125) were measured in controls and pancreatic cancer patients at the time of diagnosis and after treatment. The role of cancer cell produced type IV collagen was studied in human pancreatic cancer cell lines by functional blocking of integrin receptors (integrin a1, a2 and b1) and integrin-binding sites on type IV collagen, and by siRNA-induced down-regulation of type IV collagen synthesis. Proliferation was analyzed by a luminescence based cell viability assay, migration by time-lapse microscopy, and apoptosis by M30-neoepitope detection. Results: MMPs involved in BM degradation were upregulated in pancreatic cancer tissue. The expression of type XVIII collagen shifted from a general BM expression pattern in normal tissue, to mainly being found in the tumor vasculature in pancreatic cancer. Type IV collagen, on the other hand, remained highly expressed in the vicinity of the cancer cells. The a1, a2, and b1 integrin receptors were highly expressed at the cancer cell surface. Both down-regulation of type IV collagen synthesis and blocking the integrin/type IV collagen interaction decreased cell proliferation and migration. The proliferative capacity was rescued by the addition of exogenous type IV collagen. Furthermore, the circulating levels of both type IV and type XVIII collagen were increased in pancreatic cancer patients at the time of diagnosis compared to controls. After treatment, the levels were normalized for type XVIII collagen, whereas the levels of type IV collagen remained high after surgery. High postoperative levels of type IV collagen were associated with short overall survival. A similar association to short survival was found for preoperative type XVIII collagen levels. No such associations to survival could be detected for the conventional markers. Conclusion: The results of this thesis show that type IV and type XVIII collagens can serve as tumor markers for pancreatic cancer with advantages compared to conventionally used markers. Additionally, evidence is provided of an autocrine loop, involving type IV collagen and its integrin receptors, with importance for retaining a proliferative and migratory phenotype in pancreatic cancer cells.
36
Germundsson, Johan. „Surgical outcomes of phototherapeutic keratectomy on Epithelial basement membrane dystrophy, and the characterisation of Bowman´s Layer“. Doctoral thesis, Linköpings universitet, Avdelningen för neurovetenskap, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-106248.
Annotation:
Background. Epithelial basement membrane dystrophy (EBMD) is a common disease of the anterior cornea that can lead to problems with vision and/or painful recurrent erosions of the corneal epithelium. Several treatment options have been used, but recurrence of EBMD after treatment is a problem. Excimer laser phototherapeutic keratectomy (PTK) has become an increasingly popular surgical option in recent years due to its accuracy, reproducibility, and good clinical outcomes. When treating EBMD with PTK, the anterior corneal structures including the epithelium, Bowman´s layer (BL), and subbasal nerves are disrupted or removed completely. Little is known about how BL, nerves, and the stroma recover after PTK treatment, or how they could influence recurrence of EBMD symptoms. Additionally, very little is known about the properties and actual thickness of BL in-vivo. Aims. To improve the understanding and management of EBMD by investigating the clinical diagnosis and treatment of EBMD and its relationship to Bowman´s layer. Method. An excimer laser was used to treat EBMD patients at the Department of Ophthalmology during the period 2001-2010. IVCM was used to perform pre- and postoperative examinations. In particular, images of anterior corneal structures, cells, and nerves in high-resolution were obtained. Additionally, a group of over 100 healthy volunteers underwent a full ophthalmic examination including IVCM. Other subjects examined in this work included a group of 17 patients who underwent full-thickness transplantation of the cornea. Results and conclusions. Clinical follow-up revealed that PTK is an effective method of alleviating the clinical symptoms of EBMD, but the dystrophy can recur with time. Recurrence can be divided into clinical and morphologic types, and may depend upon treatment parameters including the type and depth of ablation. IVCM was found to be a useful screening tool pre- and postoperatively, and could prevent patients with symptoms, but no visible signs of EBMD on slit lamp examination, to go undiagnosed and untreated. BL was found to play a role in regenerative wound healing after PTK, and was also found to be important regarding the treatment and recurrence of EBMD. BL may present a physical barrier that protects the subepithelial nerve plexus thereby facilitating sensory recovery, and BL may also serve as a barrier that prevents direct traumatic contact with the corneal stroma, avoiding a stromal wound healing response. To aid in accurate assessment of BL in patients, an in vivo method for determining BL thickness was developed. This method could be an important tool to aid in clinical assessment and planned treatments of the anterior cornea. Using this tool, a large inter-individual variability in BL thickness and a strong negative correlation of BL thickness with age were found in a healthy population. Using IVCM, it was also found that subbasal nerves are pathologically reduced in EBMD compared to a healthy population, and that this nerve deficit does not improve in the long term after PTK treatment.
37
Klaentschi, Karel. „The use of Matrigel for in vitro studies of basement membrane permeability under static and dynamic pressures“. Thesis, University of Exeter, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.337744.
38
Leow, Chon Kar. „The long-term metabolic function of pancreatic islet grafts and the effect on glomerular basement membrane thickness“. Thesis, University of Bristol, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.358194.
39
Kumar, Tarun. „The role of the basement membrane and its receptors in the morphogenesis of the Drosophila Malpighian tubules“. Thesis, University of Cambridge, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708732.
40
Morss, Alisa Sharon. „Endothelial cells and basement membrane : a co-regulatory unit for fibroblast growth factor-2 in hyperglycemic stress“. Thesis, Massachusetts Institute of Technology, 2006. http://hdl.handle.net/1721.1/36167.
Annotation:
Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2006.Includes bibliographical references.
Endothelial cells and basement membrane interact as a biochemical and mechanical co-regulatory unit. The wide spectrum of manifestations of diabetic vascular disease could be related to altered kinetics of vasoactive compounds within this regulatory unit. We hypothesized that hyperglycemic stress mediates storage, release, and function of fibroblast growth factor-2 (FGF-2) through changes in interaction between endothelial cells and basement membrane. We discovered that basement membrane associated FGF-2 increased linearly with culture glucose concentration. Using novel assays, we demonstrated that FGF-2 binding kinetics were surprisingly unchanged over a range of basement membrane culture glucose. Instead, the combination of increased endothelial cell apoptosis-associated FGF-2 release and enhanced endothelial cell permeability allowed more FGF-2 to bind into the basement membrane. Such high levels of basement membrane FGF-2 abrogated the effects of hyperglycemia on proliferation but not apoptosis. An FGF-2 stimulus returned endothelial cell proliferation close to euglycemic levels, but increased apoptosis was still evident as FGF-2 signaling down an intracellular survival pathway was inhibited by glucose.
(cont.) These same findings were confirmed in vivo where FGF-2 levels were elevated in the aortic subendothelial space of diabetic animals. This thesis suggests a new paradigm for active cellular control of basement membrane and indicates the complexities of growth factor signaling in endothelial cells. Characterization of the interaction between endothelial cells and basement membrane in health and disease may advance our understanding of diabetic vascular disease and lead to development of novel biomimetic materials for therapeutic intervention.
by Alisa Sharon Morss.
Ph.D.
41
Francis, Michael. „RECAPITULATING OSTEOBLASTOGENESIS WITH ELECTROSPUN FIBRINOGEN NANOFIBERS AND ADIPOSE STEM CELLS AND ELECTROSPINNING ADIPOSE TISSUE-DERIVED BASEMENT MEMBRANE“. VCU Scholars Compass, 2010. http://scholarscompass.vcu.edu/etd/2025.
Annotation:
To repair, replace, or regenerate damaged or diseased tissue has been a long-standing, albeit elusive, goal in medical research. Here, we characterize patient-derivable mesenchymal stem cell types, termed adipose-derived stem cells (ASCs). These cells, which can be derived from liposuction fat and lipoaspirate saline, are sources for patient-derivable extracellular matrix (ECM), fibrinogen (Fg) and adipose tissue extracellular matrix, and may prove useful for synthesizing new bone tissue analogues in vitro. Traditionally and rapidly isolated ASCs were thoroughly characterized as multipotent, having osteogenic, adipogenic, and chondrogenic differentiation potential, and they exhibited comparable proliferative lifespans. These ASCs also shared an indistinguishable immunophenotype when compared to bone marrow-derived mesenchymal stem cells, suggesting that these cells are an excellent source for bone following tissue engineering experimentation. In order to synthesize bone ex-vivo, electrospun scaffolds of fibrinogen (Fg), polydioxanone (PDO), and Fg:PDO blends were seeded with early passage ASCs, fibroblasts, or osteosarcoma cells and were maintained for 21 days in osteogenic or regular growth media. Constructs were analyzed both histologically and molecularly for evidence of osteoblastogenesis. Using SEM, the appearance of regular, mineralized-appearing structures were found in osteogenic-induced ASC seeded scaffolds beyond 14 days, only in the scaffolds containing Fg. Further, at 21 days of culture, Fg scaffolds with ASCs in osteogenic media became hard and brittle. Robust new collagen synthesis and matrix remodeling were observed on all Fg scaffolds, the levels of which were elevated over time. Pronounced mineralization was found throughout bone-induced ASC scaffolds, while control scaffolds (BJ foreskin fibroblasts) showed no mineral deposition (although they did demonstrate excellent cellularity). Analysis of gene expression (qRT-PCR) indicated that electrospun Fg supported osteoblastogenesis through the upregulation of alkaline phosphatase and osteocalcin gene expression. To confirm our gene expression results, osteogenic-induced ASCs on Fg scaffolds were also shown to secrete osteocalcin in the extracellular matrix, a key marker in osteoblastogenesis. Thus, electrospun Fg is an excellent material for ASC growth, proliferation, and osteogenic differentiation, providing an ideal system for furthering basic bone model-based research and for advancing regenerative medicine. In addition to establishing Fg as a source of scaffolding, we developed and characterized a novel method for isolating and subsequently electrospinning adipose tissue matrix. Because adipose ECM contains many primordial matrix proteins important for embryonic development and regeneration (such as laminin, type IV collagen, and fibronectin), adipose ECM may prove to be an autologous tissue engineering matrix and stem cell culture substrate. We show here that adipose tissue ECM can, in fact, be electrospun into a nanofiberous mesh, histologically shown to contain connective tissue, collagens, elastic fibers/elastin, proteoglycans, and glycoproteins in the newly synthesized matrix. We also show that this novel electrospun adipose tissue scaffold is capable of supporting stem cell growth. Taken together, experiments using ASCs cultured on extracellular matrices of electrospun Fg or adipose ECM present an excellent framework for future advances in regenerative medicine therapeutics and research.
42
Kurz, Angela [Verfasser], und Markus [Akademischer Betreuer] Sperandio. „MST1 kinase is critical for neutrophil transmigration through the vascular basement membrane / Angela Kurz ; Betreuer: Markus Sperandio“. München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2016. http://d-nb.info/1117473902/34.
43
Cox, Melissa Luanne. „Identification of a mutation in COL4A5 causative for X-linked Alport syndrome in the domestic dog and analysis of gene expression in the kidneys of affected and nonaffected siblings“. Diss., Texas A&M University, 2003. http://hdl.handle.net/1969.1/244.
Annotation:
The domestic dog, Canis lupus familiaris, plays many roles in the lives of humans. Additionally, the dog is recognized for its potential as a model for many human hereditary diseases. Thus, the genetics and genomics of the dog are being studied extensively in order to facilitate its use as a model, as well as to help the dog for its own sake. As part of this research effort, our laboratory has added type I markers (i.e., the acidic and basic keratins, c-kit, type I and IV collagens, and the gene encoding uromodulin) to the emerging map of the canine genome. The mapping of genes, particularly those in large gene families such as the collagens, is valuable because it rapidly increases the density of gene loci on the map and provides insight regarding conservation of synteny between the dog and other mammals. The major focus of work reported here is the genetics of X-linked Alport syndrome (XLAS), a terminal renal disease that affects the human and the dog. The disease results from mutations in COL4A5, a type IV collagen gene. Reported here are the 1) sequencing and mapping of the canine cDNA encoding uromodulin, 2) mapping of the type I and type IV collagen genes, 3) sequencing of the full-length cDNA of canine COL4A5, 4) identification of a 10 bp deletion in COL4A5, causative for XLAS in our colony of mixed breed dogs, 5) development of a genetic test for identification of affected and carrier dogs in the colony and 6) assessment of gene expression in the kidneys of normal and XLAS-dogs. This assessment was performed using a canine-specific oligonucleotide microarray. XLAS dogs demonstrated up-regulation of many genes involved in extracellular matrix reorganization, cell structure, and immune response, as expected in a glomerulopathy with tubulointerstitial nephritis. Trends were verified by quantitative RT-PCR. A review of the current status of canine genetics research, and current understanding of hereditary diseases in the dog, concludes this dissertation.
44
Muona, A. (Anu). „Type XV collagen:complete structures of the human COL15A1 and mouse Col15a1 genes, location of type XV collagen protein in mature and developing mouse tissues, and generation of mice expressing truncated type XV collagen“. Doctoral thesis, University of Oulu, 2001. http://urn.fi/urn:isbn:9514265858.
Annotation:
Abstract
This study was initiated to elucidate the complete genomic structures of type XV
collagen in man and mouse and the functional properties of their promoters, as well as to
obtain knowledge of the biological role of type XV collagen during development and
maturity using immunofluorescence and transgenic techniques.
The cloning and characterization of genomic clones revealed that the human
COL15A1 gene is 145-kb in size and consists of 42 exons, and the
mouse Col15a1 gene is 110-kb with 40 exons. The genomic organization
of the two genes was found to be highly conserved, except for two regions of divergence.
The nuclease S1 protection analysis revealed multiple transcription initiation sites in
both genes, which is in accordance with the overall genomic structures of their
5'-flanking sequences. Transient cell transfection experiments with varying lengths of
5'-deletion constructs identified the fragments necessary for basic promoter activity in
both genes and those implicated in the positive and negative regulation of the mouse
Col15a1 gene. Furthermore, the involvement of transcription factor
Sp1 in the gene regulation of the human COL15A1 gene was demonstrated. A mouse specific
polyclonal antibody against type XV collagen was generated and utilized in the
localization of type XV collagen protein in developing and mature mouse tissues. Type XV
collagen was deposited early in the development and was particularly prominent in
capillaries. Spatio-temporal differences in the expression of type XV collagen in various
capillary types was demonstrated. Early expression was also detected in the skeletal
muscle and peripheral nerves, while expression in the heart, lung, and kidney appeared to
be developmentally regulated. Transgenic mice lines expressing truncated type XV collagen
driven by either short or long endogenous type XV collagen promoters were generated. The
two promoters conferred different tissue-specificities and expression levels, the longer
one resulting in more endogenous-like expression. Despite some expression at both mRNA
and protein levels, the truncated type XV collagen did not cause any obvious phenotypic
or histological changes in any of the lines driven by the shorter promoter fragment. In
heterozygote matings of one of the lines driven by the longer promoter fragment, however,
a portion of the transgene positive mice appeared to be lost prenatally. Furthermore,
pregnancy terminations in this line indicated a high number of abortions beginning at
about 11 days of development. Further studies are needed before detailed conclusions on
the consequences of the generated mutation can be drawn.
The elucidation of the genomic structure of the human
COL15A1 gene provides the necessary database for screening mutations
in patient samples for candidate diseases caused by this collagen. The genomic clones and
the mouse-specific antibody against type XV collagen are valuable tools also in future
projects. The knowledge of the developmental dynamics of type XV collagen is of great
value, as it helps to understand the physiological consequences that the as yet
unidentified mutations in type XV collagen may cause in humans.
45
Kinnunen, A. (Aino). „Collagen XVIII regulates basement membrane integrity:specific effects of its isoforms on the choroid plexus, kidney and hair follicle“. Doctoral thesis, Oulun yliopisto, 2011. http://urn.fi/urn:isbn:9789514294112.
Annotation:
Abstract Collagen XVIII is a multidomain basement membrane proteoglycan with three tissue-specific isoforms. Endostatin, the C-terminal part of collagen XVIII, has antiangiogenic properties, while the frizzled-like domain of the longest isoform is suggested to be capable of inhibiting the Wnt/β-catenin signaling network. This study utilized several genetically modified mouse lines and electron microscopy to achieve new information on the biological role of collagen XVIII, its different isoforms, and the frizzled domain. Lack of collagen XVIII was found to affect the integrity of basement membranes of various tissues, leading to an abnormally loosened network structure. In the choroid plexus, the change in the basement membrane ultrastructure caused alterations in the production of the cerebrospinal fluid and predisposed to the development of hydrocephalus. In the kidney, broadening of the proximal tubular basement membrane was shown to be due specifically to the lack of the short isoform, while the lack of the two longer isoforms led to podocyte foot process effacement. Moreover, lack of collagen XVIII was found to cause softening of the kidney glomeruli and the levels of serum creatinine were elevated in the mutant animals, indicating altered kidney function. The hair follicle cycle was used as a model to study the possible role of the frizzled domain of collagen XVIII in the Wnt/β-catenin signaling cascade. The longer collagen XVIII isoforms were shown to be expressed in the basement membrane facing the dermal papilla and in the hair follicle bulge, containing the follicular stem cells. Lack of the long isoforms led to abnormalities in the progression of the first hair cycle, and the phenotype could be rescued via transgenic delivery of the frizzled domain of the longest isoform, suggesting its involvement in the regulation of the Wnt/β-catening signaling network during the cyclic growth of the hairTiivistelmä Kollageeni XVIII on useista toiminnallisista osista koostuva tyvikalvojen proteoglykaani, jolla on kolme eri kudoksissa esiintyvää isomuotoa. Sen C-terminaalisella endostatiini-osalla on verisuonten kasvua estäviä vaikutuksia, kun taas pisimmän isomuodon frizzled-osan uskotaan estävän Wnt/β-kateniini signalointireitin toimintaa. Tässä tutkimuksessa saatiin uutta tietoa kollageeni XVIII:n, sen eri isomuotojen sekä frizzled-osan biologisesta merkityksestä useiden geenimuunneltujen hiirimallien sekä elektronimikroskopian avulla. Kollageeni XVIII:n puutoksen todettiin vaikuttavan tyvikalvojen rakenteen eheyteen useissa eri kudoksisssa, johtaen epänormaalisti löyhtyvään verkkorakenteeseen. Suonipunoksessa tämä tyvikalvon hienorakenteen muutos vaikutti aivo-selkäydinnesteen tuottumiseen ja altisti vesipään kehittymiselle. Munuaisessa proksimaalisen munuaistiehyen tyvikalvon levenemisen osoitettiin johtuvan lyhyen isomuodon puutoksesta, kun taas kahden pidemmän isomuodon puuttuminen aiheutti podosyyttien jalkalisäkkeiden leviämistä. Lisäksi kollageeni XVIII:n puuttumisen osoitettiin johtavan hiirimallien munuaiskerästen pehmenemiseen sekä veren kreatiniinitason kohoamiseen, viitaten munuaistoiminnan häiriöihin. Karvatuppien syklistä kasvua käytettiin mallina tutkittaessa kollageeni XVIII:n frizzled-osan mahdollisia vaikutuksia Wnt/β-kateniini signalointireittiin. Pidempien kollageeni XVIII isomuotojen osoitettiin tuottuvan karvanystyn tyvikalvossa sekä karvatupin kantasolut sisältävällä pullistuma-alueella. Pitkien isomuotojen puuttuminen johti karvojen ensimmäisen kasvukierron epänormaaliin etenemiseen. Tämä voitiin estää siirtogeenisen frizzled-osan avulla, mikä viittasi sen osallisuuteen Wnt/β-kateniini signalointireitin säätelyyn karvan syklisen kasvun aikana
46
Fowler, Susan J. „Molecular analysis of glucose-induced basement membrane thickening in hydra vulgaris : a non-mammalian model for diabetic microangiopathy“. Thesis, University of Manchester, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.706484.
47
Glentis, Alexandros. „Le rôle des fibroblastes associés aux carcinomes dans l’invasion de la membrane basale par les cellules cancéreuses“. Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066452.
Annotation:
La membrane basale (BM) constitue une barrière physiologique entre les tissus et leur microenvironnement. Dans le cas des cancers épithéliaux, au stade de carcinome invasif, la membrane basale est compromise et les cellules cancéreuses envahissent le stroma. Dans cette thèse de doctorat, j’ai proposé d’étudier l’invasion de la membrane basale par les cellules cancéreuses et comment une population de cellules stromales, les fibroblastes, affectent cette invasion. Dans le cadre de cette étude, nous avons utilisé le modèle du cancer colorectal. En collaboration avec l’hôpital Curie, nous avons isolé des fibroblastes à partir de tumeurs de patients opérés. On a nommé les fibroblastes isolés de la partie tumorale « CAF » et ceux venant de la partie du tissu normal, à proximité de la tumeur, « NAF ». Comme modèle de BM nous avons utilisé le mésentère de souris. Afin étudier l’invasion des cellules cancéreuses à travers le mésentère et l’effet des fibroblastes, nous avons mis en place une construction en 3D in vitro. Nous avons montré que les CAFs, et rarement les NAFs, induisent l’invasion des cellules cancéreuse et que cet effet est prononcé quand les CAFs sont physiquement présents sur la membrane. En faisant une étude protéomique comparative entre CAFs et NAFs, on a montré que les CAF expriment plus de protéines composantes de la membrane basale, des protéines impliqués dans le remodelage de la matrice extracellulaire, et des protéines impliquées dans la contraction des cellules. Nous avons ensuite voulu comprendre par quel mécanisme les CAFs induisent l’invasion. Nous avons montré qu’en présence des CAFs, l’invasion ce fait de façon indépendante des métaloprotéinases mais que l’effet contractif des CAFs est nécessaire. En conclusion, l’ensemble de ces résultats mets en évidence l’effet promoteur des CAFs sur l’invasion des cellules cancéreuses et souligne l’importance de leur contractilité dans ce mécanismeBasement membrane represents a physiological barrier between epithelial tissues and their microenvironment. In invasive carcinomas, the membrane is breached and cancer cells disseminate in the stroma. In this PhD thesis, I investigated how cancer cells breach the BM and whether a stromal cell population, fibroblasts, assist them in that process. I used colorectal cancer as a model. In collaboration with the Institut Curie Hospital, we isolated human primary fibroblasts from human colorectal cancers, called CAFs and the adjacent normal tissue, NAFs. To study BM invasion, I developed a 3D in vitro assay based on the mouse mesentery. We showed that CAFs, and rarely NAFs, induce cancer cell invasion. This pro-invasive effect is mainly mediated when CAFs are physically present on the membrane, rather than through paracrine ways. To understand how CAFs facilitate invasion, we performed a proteomic comparison between cancer cell-stimulated CAFs and NAFs. Results showed that CAFs produced more proteins-components of the ECM, matrix remodelers and they were more contractile compared to NAFs. Further, we wished to understand the mechanism by which CAFs mediate their effect. We showed that CAFs can induce invasion in a MMP independent way. However, Inhibition of contractility abolished CAFs capacity to induce invasion. Dynamic analysis of cancer cells-fibroblasts co-cultures showed that CAFs could pull on the BM fibers. To directly test this possibility, we created holes in the BM using laser ablations. While in the presence of cancer cells alone, holes remained the same size, in the presence of CAFs, holes widen over time. We further showed that this mechanism is MMP independent but depends on contractility. Altogether, these results demonstrate that CAFs stimulate cancer cell invasion through BM by acting directly on the BM, possibly by depositing ECM components and proteins that remodel ECM and by exerting physical forces on the membrane by contraction
48
Mazariegos, Mario Rolando. „Biogenesis of basement membrane components by the endodermal cells of the rat parietal yolk sac as studied by radioautography“. Thesis, McGill University, 1986. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=66113.
49
Mohamed, Alahlafi Abdelaziz H. „The significance of immune reactants deposited in the basement membrane zone of the skin in patients with lupus erythematosus“. Thesis, University of Oxford, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.275408.
50
Powers, Nathan Anthony. „Involvement of JAK/STAT Signaling and a Basement Membrane-Associated Protein during Air Sac Primordium Development in Drosophila Melanogaster“. TopSCHOLAR®, 2018. https://digitalcommons.wku.edu/theses/3089.
Annotation:
Tumor metastasis currently presents the greatest obstacle for effective cancer remediation. Metastatic growth necessitates both degradation of a specialized form of extracellular matrix (ECM) known as the basement membrane (BM) and the invasion of surrounding tissues thereafter. The thoracic air sacs of fruit flies (Drosophila melanogaster), which develop and operate in a fashion comparable to the human lung, provide a unique model for identifying and characterizing factors that contribute to its own development as well as tumoral invasion. We investigated the involvement of both Janus kinase (JAK)/Signal transducer and activator of transcription (STAT) signaling and a BMassociated protein during the development of air sac primordia (ASPs), the precursors to Drosophila air sacs. We find that JAK/STAT signaling occurs in ASP tip cells and that misexpression of core pathway components via the GAL4/UAS system negatively impacts ASP development. Further, we identify Unpaired 2 (Upd2) as the primary activating ligand for JAK/STAT activity in the ASP. Knockdown of the BM-associated protein using GAL4 drivers associated with a fibroblast growth factor (FGF) receptor gene, breathless (btl), and segment polarity gene, patched (ptc), prevented larval development beyond the second larval instar (L2). Knockdown of the BM-associated protein in the wing also produced bristle defects, but its overexpression did not have an effect anywhere other than in the ASP, where the proportion of mutant phenotypes increased significantly (p < .0001) in response. Finally, we find that collagen IV localization was unaffected by knockdown of the BM-associated protein. Together, our data constitute a significant step forward in understanding the role of both this BM-associated protein and JAK/STAT signaling in the ASP and similar mammalian structures.