期刊
MOLECULAR THERAPY
卷 30, 期 4, 页码 1741-1753出版社
CELL PRESS
DOI: 10.1016/j.ymthe.2021.10.013
关键词
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资金
- National Natural Science Foundation of China [82000810, 81970720, 81870567, 81800731]
- Science and Technology Research Program of Chongqing Municipal Education Commission [KJZD-K202000401]
- NIH [R01 DK117913, 1R01DK078897, 1R01DK088541, P01-DK56492]
This study utilizes single-cell RNA sequencing to reveal the specific responses of kidney cells to ARBs and SGLT2i, and identifies a novel PT subcluster that plays a significant role in DKD.
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 mitochondria) 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.
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