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dc.contributor.authorRandles, Michael
dc.contributor.authorLausecker, Franziska
dc.contributor.authorKong, Qingyang
dc.contributor.authorSuleiman, Hani
dc.contributor.authorReid, Graeme
dc.contributor.authorKolatsi-Joannou, Maria
dc.contributor.authorDavenport, Bernard
dc.contributor.authorTian, Pinyuan
dc.contributor.authorFalcone, Sara
dc.contributor.authorPotter, Paul
dc.contributor.authorVan Agtmael, Tom
dc.contributor.authorNorman, Jill T.
dc.contributor.authorLong, David A.
dc.contributor.authorHumphries, Martin J.
dc.contributor.authorMiner, Jeffrey H.
dc.contributor.authorLennon, Rachel
dc.date.accessioned2022-08-02T09:10:24Z
dc.date.available2022-08-02T09:10:24Z
dc.date.issued2021-06-30
dc.identifierhttps://chesterrep.openrepository.com/bitstream/handle/10034/627062/1713.full.pdf?sequence=1
dc.identifier.citationMichael J. Randles, M. J., Lausecker, F., Kong, Q., Suleiman, H., Reid, G., Kolatsi-Joannou, M., Davenport, B., Tian, P., Falcone, S., Potter, P., Van Agtmael, T., Norman, J. T., Long, D. A., Humphries, M. J., Miner, J. H., & Lennon, R. (2021). Identification of an altered matrix signature in kidney aging and disease. Journal of the American Society of Nephrology, 32(7), 1713-1732. https://doi.org/10.1681/ASN.2020101442en_US
dc.identifier.issn1046-6673
dc.identifier.doi10.1681/ASN.2020101442
dc.identifier.urihttp://hdl.handle.net/10034/627062
dc.description.abstractBackground: Accumulation of extracellular matrix in organs and tissues is a feature of both aging and disease. In the kidney, glomerulosclerosis and tubulointerstitial fibrosis accompany the decline in function, which current therapies cannot address, leading to organ failure. Although histologic and ultrastructural patterns of excess matrix form the basis of human disease classifications, a comprehensive molecular resolution of abnormal matrix is lacking. Methods: Using mass spectrometry–based proteomics, we resolved matrix composition over age in mouse models of kidney disease. We compared the changes in mice with a global characterization of human kidney matrix during aging and to existing kidney disease datasets to identify common molecular features. Results: Ultrastructural changes in basement membranes are associated with altered cell adhesion and metabolic processes and with distinct matrix proteomes during aging and kidney disease progression in mice. Within the altered matrix, basement membrane components (laminins, type IV collagen, type XVIII collagen) were reduced and interstitial matrix proteins (collagens I, III, VI, and XV; fibrinogens; and nephronectin) were increased, a pattern also seen in human kidney aging. Indeed, this signature of matrix proteins was consistently modulated across all age and disease comparisons, and the increase in interstitial matrix was also observed in human kidney disease datasets. Conclusions: This study provides deep molecular resolution of matrix accumulation in kidney aging and disease, and identifies a common signature of proteins that provides insight into mechanisms of response to kidney injury and repair.en_US
dc.publisherAmerican Society of Nephrologyen_US
dc.relation.urlhttps://jasn.asnjournals.org/content/32/7/1713/tab-article-infoen_US
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/34049963/
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.subjectExtracellular matrixen_US
dc.subjectbasement membraneen_US
dc.subjectmass spectrometryen_US
dc.subjectproteomicsen_US
dc.subjecttubulointerstitiumen_US
dc.subjectfibrosisen_US
dc.subjectmatrix signatureen_US
dc.subjectnephronectinen_US
dc.subjecttype IV collagenen_US
dc.titleIdentification of an Altered Matrix Signature in Kidney Aging and Diseaseen_US
dc.typeArticleen_US
dc.identifier.eissn1533-3450en_US
dc.contributor.departmentThe University of Manchester; University College London; Washington University; Manchester Royal Infirmary; University of Oxford; Oxford Brookes University; University of Glasgow; Royal Manchester Children’s Hospital; University of Chesteren_US
dc.identifier.journalJournal of the American Society of Nephrologyen_US
or.grant.openaccessYesen_US
rioxxterms.funderWellcome Trusthttps://doi.org/10.13039/ 100004440 Senior Fellowship Award 202860/Z/16/Zen_US
rioxxterms.identifier.projectWellcome Trusthttps://doi.org/10.13039/ 100004440 Senior Fellowship Award 202860/Z/16/Zen_US
rioxxterms.versionVoRen_US
rioxxterms.versionofrecord10.1681/ASN.2020101442en_US
dcterms.dateAccepted2021-03-22
rioxxterms.publicationdate2021-06-30
dc.date.deposited2022-08-02en_US
dc.indentifier.issn1046-6673en_US


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