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

Lay, Abigail C. ; Tran, Van Du T. ; Nair, Viji ; Betin, Virginie ; Hurcombe, Jennifer A. ; Barrington, Alexandra F. ; Pope, Robert J.P. ; Burdet, Frédéric ; Mehl, Florence and Kryvokhyzha, Dmytro LU orcid , et al. (2024) In Nature Communications 15(1).
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... (More)

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.

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author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
15
issue
1
article number
10018
publisher
Nature Publishing Group
external identifiers
  • pmid:39562547
  • scopus:85209996664
ISSN
2041-1723
DOI
10.1038/s41467-024-54089-1
language
English
LU publication?
yes
id
b31cb7ba-6bbd-4d12-a0d2-4153319ff3d3
date added to LUP
2025-01-08 15:42:06
date last changed
2025-07-10 20:11:46
@article{b31cb7ba-6bbd-4d12-a0d2-4153319ff3d3,
  abstract     = {{<p>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.</p>}},
  author       = {{Lay, Abigail C. and Tran, Van Du T. and Nair, Viji and Betin, Virginie and Hurcombe, Jennifer A. and Barrington, Alexandra F. and Pope, Robert J.P. and Burdet, Frédéric and Mehl, Florence and Kryvokhyzha, Dmytro and Ahmad, Abrar and Sinton, Matthew C. and Lewis, Philip and Wilson, Marieangela C. and Menon, Rajasree and Otto, Edgar and Heesom, Kate J. and Ibberson, Mark and Looker, Helen C. and Nelson, Robert G. and Ju, Wenjun and Kretzler, Matthias and Satchell, Simon C. and Gomez, Maria F. and Coward, Richard J.M. and Ju, Wenjun}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Profiling of insulin-resistant kidney models and human biopsies reveals common and cell-type-specific mechanisms underpinning Diabetic Kidney Disease}},
  url          = {{http://dx.doi.org/10.1038/s41467-024-54089-1}},
  doi          = {{10.1038/s41467-024-54089-1}},
  volume       = {{15}},
  year         = {{2024}},
}