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

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

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  • Media type: E-Article
  • Title: Single-cell transcriptomics reveals a mechanosensitive injury signaling pathway in early diabetic nephropathy
  • Contributor: Liu, Shuya; Zhao, Yu; Lu, Shun; Zhang, Tianran; Lindenmeyer, Maja T.; Nair, Viji; Gies, Sydney E.; Wu, Guochao; Nelson, Robert G.; Czogalla, Jan; Aypek, Hande; Zielinski, Stephanie; Liao, Zhouning; Schaper, Melanie; Fermin, Damian; Cohen, Clemens D.; Delic, Denis; Krebs, Christian F.; Grahammer, Florian; Wiech, Thorsten; Kretzler, Matthias; Meyer-Schwesinger, Catherine; Bonn, Stefan; Huber, Tobias B.
  • Published: Springer Science and Business Media LLC, 2023
  • Published in: Genome Medicine, 15 (2023) 1
  • Language: English
  • DOI: 10.1186/s13073-022-01145-4
  • ISSN: 1756-994X
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>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.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>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 <jats:italic>ob/ob</jats:italic>) at the early stage of DN.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>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.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Overall, our study presents a comprehensive single-cell transcriptomic landscape of early DN, highlighting mechanosensitive signaling pathways as novel targets of diabetic glomerulopathy.</jats:p> </jats:sec>
  • Access State: Open Access