Skip to Content
MilliporeSigma
  • Single-cell transcriptomics reveals a mechanosensitive injury signaling pathway in early diabetic nephropathy.

Single-cell transcriptomics reveals a mechanosensitive injury signaling pathway in early diabetic nephropathy.

Genome medicine (2023-01-11)
Shuya Liu, Yu Zhao, Shun Lu, Tianran Zhang, Maja T Lindenmeyer, Viji Nair, Sydney E Gies, Guochao Wu, Robert G Nelson, Jan Czogalla, Hande Aypek, Stephanie Zielinski, Zhouning Liao, Melanie Schaper, Damian Fermin, Clemens D Cohen, Denis Delic, Christian F Krebs, Florian Grahammer, Thorsten Wiech, Matthias Kretzler, Catherine Meyer-Schwesinger, Stefan Bonn, Tobias B Huber
ABSTRACT

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, and histopathologic glomerular lesions are among the earliest structural alterations of DN. However, the signaling pathways that initiate these glomerular alterations are incompletely understood. To delineate the cellular and molecular basis for DN initiation, we performed single-cell and bulk RNA sequencing of renal cells from type 2 diabetes mice (BTBR ob/ob) at the early stage of DN. Analysis of differentially expressed genes revealed glucose-independent responses in glomerular cell types. The gene regulatory network upstream of glomerular cell programs suggested the activation of mechanosensitive transcriptional pathway MRTF-SRF predominantly taking place in mesangial cells. Importantly, activation of MRTF-SRF transcriptional pathway was also identified in DN glomeruli in independent patient cohort datasets. Furthermore, ex vivo kidney perfusion suggested that the regulation of MRTF-SRF is a common mechanism in response to glomerular hyperfiltration. Overall, our study presents a comprehensive single-cell transcriptomic landscape of early DN, highlighting mechanosensitive signaling pathways as novel targets of diabetic glomerulopathy.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Protease from Bacillus licheniformis, Type VIII, lyophilized powder, 7-15 units/mg solid
Sign Into View Organizational & Contract Pricing
SKUPack SizeAvailabilityPriceQuantity
1 g
Estimated to ship on March 24, 2025
$53.20
5 g
Estimated to ship on March 24, 2025
$208.00
10 g
Estimated to ship on March 24, 2025
$431.00