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Abstract
Diabetic kidney disease (DKD) is the leading cause of end stage kidney failure worldwide, of which cellular insulin resistance is a major driver. Here, we study key human kidney cell types implicated in DKD (podocytes, glomerular endothelial, mesangial and proximal tubular cells) in insulin sensitive and resistant conditions, and perform simultaneous transcriptomics and proteomics for integrated analysis. Our data is further compared with bulk- and single-cell transcriptomic kidney biopsy data from early- and advanced-stage DKD patient cohorts. We identify several consistent changes (individual genes, proteins, and molecular pathways) occurring across all insulin-resistant kidney cell types, together with cell-line-specific changes occurring in response to insulin resistance, which are replicated in DKD biopsies. This study provides a rich data resource to direct future studies in elucidating underlying kidney signalling pathways and potential therapeutic targets in DKD.
Original language | English |
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Article number | 10018 |
Number of pages | 19 |
Journal | Nature Communications |
Volume | 15 |
Issue number | 1 |
Early online date | 19 Nov 2024 |
DOIs | |
Publication status | E-pub ahead of print - 19 Nov 2024 |
Bibliographical note
Publisher Copyright:© The Author(s) 2024.
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Dive into the research topics of 'Profiling of insulin-resistant kidney models and human biopsies reveals common and cell-type-specific mechanisms underpinning Diabetic Kidney Disease'. Together they form a unique fingerprint.Projects
- 1 Finished
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Is Diabetic Nephropathy the Result of a Podocyte Tauopathy?
Coward , R. J. M. (Principal Investigator)
1/08/19 → 30/12/23
Project: Research