"RNA-Seq transcriptome analysis of renal tissue from spontaneously hypertensive rats revealed renal protective effects of dapagliflozin, an inhibitor of sodium-glucose cotransporter 2"

作者全名："Wei, Jiangjun; Tan, Fangyan; Long, Xianglin; Fang, Qinghua; Wang, Yao; Wang, Jing; He, JiaCheng; Yuan, Xin; Du, Jianlin"

作者地址："[Wei, Jiangjun; Long, Xianglin; Fang, Qinghua; Wang, Yao; Wang, Jing; He, JiaCheng; Du, Jianlin] Chongqing Med Univ, Affiliated Hosp 2, Dept Cardiol, Chongqing 400010, Peoples R China; [Tan, Fangyan; Yuan, Xin] Chongqing Med Univ, Affiliated Hosp 2, Dept Nephrol, Chongqing 400010, Peoples R China"

通信作者："Du, JL (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Cardiol, Chongqing 400010, Peoples R China."

来源：EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001049400900001

JCR分区：Q1

影响因子：4.3

年份：2023

卷号：189

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Hypertensive nephropathy; Dapagliflozin; RNA sequencing; Inflammation; Fibrosis; Metabolism

摘要："Hypertensive nephropathy (HTN) is a common complication of hypertension. Although various agents for treatment of hypertension exert significant effects, there is currently no effective treatment for hypertensive nephropathy. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, such as dapagliflozin (DAPA), are a new class of hypoglycemic agents shown to improve the prognosis of patients with chronic kidney disease and diabetes mellitus. However, the mechanisms underlying the protective effects of DAPA remain unclear. RNA-sequencing (RNA-Seq)-based computational analysis was conducted to explore the transcriptomic changes to spontaneously hypertensive rats (SHRs) treated with DAPA for 8 weeks. Differentially expressed genes in SHRs were related to dysregulation of lipid metabolism, oxidation-reduction reaction, immunity and inflammation in HTN. Transcriptome analysis showed that 8 weeks of DAPA therapy exerted protective effects on the renal tissues of SHRs through the lysosomal, phagosomal, and autophagic pathways. VENN diagram analysis identified Zinc finger and BTB domain-containing 20 (Zbtb20) as the potential target of DAPA therapy. Consistent with the RNA-Seq findings, real-time quantitative PCR and immunohistochemical analyses revealed increased expression of Zbtb20 in the renal tissues of SHRs, whereas expression was decreased following 8 weeks of DAPA administration. The results of this study clarified the transcriptome signature of HTN and the beneficial effects of DAPA on renal tissues by alleviating dysregulation of metabolic processes and reducing inflammation."

基金机构："Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical Uni- versity; National Natural Science Foundation of China [81900631, 82270281]; China Postdoctoral Science Foundation Grant [2019M653354]; Natural Science Foundation Postdoctoral Program of Chongqing Science and Technology Bureau [cstc2019jcyj- bsh0012]; Natural Science Foundation of Chongqing Science and Technology Commission [cstc2020jcyj-msxmX0210]; Future Medicine Youth Innovation Team Development Support Program of Chongqing Medical University [W0133]; Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University; Senior Medical Talents Program of Chongqing for Young and Middle-aged"

基金资助正文："This work was financially supported by grants from the National Natural Science Foundation of China (Grant no. 81900631; 82270281) , China Postdoctoral Science Foundation Grant (Grant no. 2019M653354) , Natural Science Foundation Postdoctoral Program of Chongqing Science and Technology Bureau (Grant no. cstc2019jcyj- bsh0012) , Natural Science Foundation of Chongqing Science and Technology Commission (Grant no. cstc2020jcyj-msxmX0210) , Future Medicine Youth Innovation Team Development Support Program of Chongqing Medical University (Grant no. W0133) , Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University, and Senior Medical Talents Program of Chongqing for Young and Middle-aged (Jianlin Du [2022] ) ."