TY - JOUR
T1 - Profiling of insulin-resistant kidney models and human biopsies reveals common and cell-type-specific mechanisms underpinning Diabetic Kidney Disease
AU - Lay, Abigail C.
AU - Tran, Van Du T.
AU - Nair, Viji
AU - Betin, Virginie
AU - Hurcombe, Jennifer A.
AU - Barrington, Alexandra F.
AU - Pope, Robert J.P.
AU - Burdet, Frédéric
AU - Mehl, Florence
AU - Kryvokhyzha, Dmytro
AU - Ahmad, Abrar
AU - Sinton, Matthew C.
AU - Lewis, Philip
AU - Wilson, Marieangela C.
AU - Menon, Rajasree
AU - Otto, Edgar
AU - Heesom, Kate J.
AU - Ibberson, Mark
AU - Looker, Helen C.
AU - Nelson, Robert G.
AU - Ju, Wenjun
AU - Kretzler, Matthias
AU - Satchell, Simon C.
AU - Gomez, Maria F.
AU - Coward, Richard J.M.
AU - Ju, Wenjun
AU - BEAt-DKD Consortium
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-024-54089-1
DO - 10.1038/s41467-024-54089-1
M3 - Article
C2 - 39562547
AN - SCOPUS:85209996664
SN - 2041-1723
VL - 15
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 10018
ER -
