Profiling of insulin-resistant kidney models and human biopsies reveals common and cell-type-specific mechanisms underpinning Diabetic Kidney Disease

Profiling of insulin-resistant kidney models and human biopsies reveals common and cell-type-specific mechanisms underpinning Diabetic Kidney Disease

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...

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Main Authors: Abigail C. Lay, Van Du T. Tran, Viji Nair, Virginie Betin, Jennifer A. Hurcombe, Alexandra F. Barrington, Robert JP Pope, Frédéric Burdet, Florence Mehl, Dmytro Kryvokhyzha, Abrar Ahmad, Matthew C. Sinton, Philip Lewis, Marieangela C. Wilson, Rajasree Menon, Edgar Otto, Kate J. Heesom, Mark Ibberson, Helen C. Looker, Robert G. Nelson, Wenjun Ju, Matthias Kretzler, Simon C. Satchell, Maria F. Gomez, Richard J. M. Coward, BEAt-DKD consortium
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-54089-1
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Summary: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.
ISSN:2041-1723

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