Identification of an Altered Matrix Signature in Kidney Aging and Disease
Authors
Randles, MichaelLausecker, Franziska
Kong, Qingyang
Suleiman, Hani
Reid, Graeme
Kolatsi-Joannou, Maria
Davenport, Bernard
Tian, Pinyuan
Falcone, Sara
Potter, Paul
Van Agtmael, Tom
Norman, Jill T.
Long, David A.
Humphries, Martin J.
Miner, Jeffrey H.
Lennon, Rachel
Affiliation
The 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 ChesterPublication Date
2021-06-30
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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.Citation
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.2020101442Publisher
American Society of NephrologyAdditional Links
https://jasn.asnjournals.org/content/32/7/1713/tab-article-infohttps://pubmed.ncbi.nlm.nih.gov/34049963/
Type
ArticleISSN
1046-6673EISSN
1533-3450ae974a485f413a2113503eed53cd6c53
10.1681/ASN.2020101442
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