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Identification of an Altered Matrix Signature in Kidney Aging and Disease
Randles, Michael Lausecker, Franziska Kong, Qingyang Suleiman, Hani Reid, Graeme Kolatsi-Joannou, Maria Davenport, Bernard Tian, Pinyuan Falcone, Sara Potter, Paul
Randles, Michael
Lausecker, Franziska
Kong, Qingyang
Suleiman, Hani
Reid, Graeme
Kolatsi-Joannou, Maria
Davenport, Bernard
Tian, Pinyuan
Falcone, Sara
Potter, Paul
Advisors
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Other Contributors
EPub Date
Publication Date
2021-06-30
Submitted Date
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Article - VoR
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Abstract
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.2020101442
Publisher
American Society of Nephrology
Journal
Journal of the American Society of Nephrology
Research Unit
DOI
10.1681/ASN.2020101442
PubMed ID
PubMed Central ID
Type
Article
Language
Description
Series/Report no.
ISSN
1046-6673
EISSN
1533-3450