Single-cell transcriptomics reveals a mechanosensitive injury signaling pathway in early diabetic nephropathy
Beteiligte Einrichtungen
Abstract
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: Overall, our study presents a comprehensive single-cell transcriptomic landscape of early DN, highlighting mechanosensitive signaling pathways as novel targets of diabetic glomerulopathy.
Bibliografische Daten
Originalsprache | Englisch |
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ISSN | 1756-994X |
DOIs | |
Status | Veröffentlicht - 10.01.2023 |
Anmerkungen des Dekanats
© 2023. The Author(s).
PubMed | 36627643 |
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