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

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

作者地址："[Wu, Jinshan; Yang, Shumin; Hu, Jinbo; Ma, Linqiang; Peng, Chuan; Wang, Zhihong; Li, Qifu] Chongqing Med Univ, Dept Endocrinol, Affiliated Hosp 1, 1 Youyi St, Chongqing 400016, Peoples R China; [Sun, Zeguo; Fu, Jia; Lee, Kyung; He, John Cijiang] Icahn Sch Med Mt Sinai, Dept Med, Div Nephrol, New York, NY 10029 USA; [Fan, Ying; Wang, Niansong] Shanghai Jiao Tong Univ, Dept Nephrol, Affiliated Peoples Hosp 6, Shanghai 200233, Peoples R China; [He, John Cijiang] James J Peters VA Med Ctr, Renal Program, Bronx, NY 10468 USA"

通信作者："Li, QF (通讯作者)，Chongqing Med Univ, Dept Endocrinol, Affiliated Hosp 1, 1 Youyi St, Chongqing 400016, Peoples R China.; He, JC (通讯作者)，Dept Med Nephrol, One Gustave L Levy Pl,Box 1243, New York, NY 10029 USA."

来源：MOLECULAR THERAPY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000784412500002

JCR分区：Q1

影响因子：12.4

年份：2022

卷号：30

期号：4

开始页：1741

结束页：1753

文献类型：Article

关键词：　

摘要："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."

基金机构："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]"

基金资助正文："ACKNOWLEDGMENTS Q.L. is supported by the National Natural Science Foundation of China (81970720, 81870567) and the Science and Technology Research Program of Chongqing Municipal Education Commission (KJZD-K202000401) . J.C.H. is supported by NIH 1R01DK078897, NIH 1R01DK088541, VA Merit Award and NIH P01-DK56492. J.H. is supported by The National Natural Science Foundation of China (81800731) . L.M. is supported by The National Natural Science Foundation of China (82000810) . K.L. is supported by NIH R01 DK117913."