Glomerular Cell Cross-Talk Influences Composition and Assembly of Extracellular Matrix

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dc.cclicenceCC-BY-NCen
dc.contributor.authorRandles, Michael J.en
dc.contributor.authorByron, Adamen
dc.contributor.authorHumphries, Jonathan D.en
dc.contributor.authorMironov, Aleksandren
dc.contributor.authorHamidi, Hellyehen
dc.contributor.authorHarris, Shelleyen
dc.contributor.authorMathieson, Peter W.en
dc.contributor.authorSaleem, Moin A.en
dc.contributor.authorSatchell, Simon C.en
dc.contributor.authorZent, Royen
dc.contributor.authorHumphries, Martin J.en
dc.contributor.authorLennon, Rachelen
dc.date.acceptance2013-12-16en
dc.date.accessioned2017-10-30T14:20:52Z
dc.date.available2017-10-30T14:20:52Z
dc.date.issued2014-01-16
dc.description.abstractThe glomerular basement membrane (GBM) is a specialized extracellular matrix (ECM) compartment within the glomerulus that contains tissue-restricted isoforms of collagen IV and laminin. It is integral to the capillary wall and therefore, functionally linked to glomerular filtration. Although the composition of the GBM has been investigated with global and candidate-based approaches, the relative contributions of glomerular cell types to the production of ECM are not well understood. To characterize specific cellular contributions to the GBM, we used mass spectrometry–based proteomics to analyze ECM isolated from podocytes and glomerular endothelial cells in vitro. These analyses identified cell type–specificdifferences in ECM composition, indicating distinct contributions to glomerular ECM assembly. Coculture of podocytes and endothelial cells resulted in an altered composition and organization of ECM compared with monoculture ECMs, and electron microscopy revealed basement membrane–like ECM deposition between cocultured cells, suggesting the involvement of cell–cell cross-talk in the production of glomerular ECM. Notably, compared with monoculture ECM proteomes, the coculture ECM proteome better resembled a tissue-derived glomerular ECM dataset, indicating its relevance to GBM in vivo. Protein network analyses revealed a common core of 35 highly connected structural ECM proteins that may be important for glomerular ECM assembly. Overall, these findings show the complexity of the glomerular ECM and suggest that both ECM composition and organization are context-dependent.en
dc.funderN/Aen
dc.identifier.citationByron A et al. (2014) Glomerular Cell Cross-Talk Influences Composition and Assembly of Extracellular Matrix. Journal of the American Society of Nephrology, 25 (5), pp. 953-966en
dc.identifier.doihttps://doi.org/10.1681/ASN.2013070795
dc.identifier.urihttp://hdl.handle.net/2086/14741
dc.language.isoenen
dc.peerreviewedYesen
dc.projectidN/Aen
dc.publisherAmerican Society of Nephrologyen
dc.researchinstituteInstitute for Allied Health Sciences Researchen
dc.subjectECMen
dc.subjectGlomerular cellsen
dc.subjectpodocytesen
dc.titleGlomerular Cell Cross-Talk Influences Composition and Assembly of Extracellular Matrixen
dc.typeArticleen

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