Kidney single-cell transcriptome profile reveals distinct response of proximal tubule cells to SGLT2i and ARB treatment in diabetic mice

Jinshan Wu, Zeguo Sun, Shumin Yang, Jia Fu, Ying Fan, Niansong Wang, Jinbo Hu, Linqiang Ma, Chuan Peng, Zhihong Wang, Kyung Lee, John Cijiang He, Qifu Li

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Angiotensin receptor blockers (ARBs) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been used as the standard therapy for patients with diabetic kidney disease (DKD). However, how these two drugs possess additive renoprotective effects remains unclear. Here, we conducted single-cell RNA sequencing to profile the kidney cell transcriptome of db/db mice treated with vehicle, ARBs, SGLT2i, or ARBs plus SGLT2i, using db/m mice as control. We identified 10 distinct clusters of kidney cells with predominant proximal tubular (PT) cells. We found that ARBs had more anti-inflammatory and anti-fibrotic effects, while SGLT2i affected more mitochondrial function in PT. We also identified a new PT subcluster, was increased in DKD, but reversed by the treatments. This new subcluster was also confirmed by immunostaining of mouse and human kidneys with DKD. Together, our study reveals kidney cell-specific gene signatures in response to ARBs and SGLT2i and identifies a new PT subcluster, which provides new insight into the pathogenesis of DKD.

Original languageEnglish
Pages (from-to)1741-1753
Number of pages13
JournalMolecular Therapy
Volume30
Issue number4
DOIs
StatePublished - 6 Apr 2022

Keywords

  • ARBs
  • SGLT2i
  • diabetic kidney disease
  • proximal tubular cells
  • scRNA-seq

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