文献类型：期刊文献

英文题名：CD3D silencing alleviates diabetic nephropathy via inhibition of JAK/STAT pathway

作者：Lei, Xianghong[1];Zou, Fangqin[1];Tang, Xianhu[1];He, Fengxia[1];Wang, Jiyang[1];Cheng, Shengyu[1];Lei, Xiangxin[2]

机构：[1]Gannan Med Univ, Affiliated Hosp 1, Dept Nephrol, Ganzhou, Peoples R China;[2]East China Univ Sci & Technol, Sch Informat Sci & Engn, 130 Meilong Rd, Shanghai, Peoples R China

年份：2024

卷号：38

期号：21

外文期刊名：FASEB JOURNAL

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001368790800001)】；

基金：Not applicable.

语种：英文

外文关键词：CD3D; diabetic nephropathy; inflammatory response; JAK/STAT; lipid metabolism

摘要：Diabetic nephropathy (DN) is a severe microvascular complication of diabetes that poses a significant burden to global health. This investigation aims to illustrate the functional role of CD3D and its relevant mechanisms in DN progression. The pivotal genes between the GSE47183 and GSE30528 datasets were identified using bioinformatics methods. The effects of CD3D silencing on renal damage, inflammatory response, and lipid metabolism were validated in DN mice. Furthermore, the impacts of CD3D knockdown on cell viability, apoptotic rate, inflammation, and lipid levels were investigated in HK-2 cells under high glucose (HG) conditions. Additionally, RO8191 was employed to investigate the role of CD3D in the JAK/STAT pathway in HG-treated cells. A total of 5 focal genes were identified through bioinformatics and were found to be upregulated in renal tissues from DN mice. CD3D silencing mitigated pathological damage to kidneys, reduced inflammatory response, and decreased lipid accumulation in DN mice. HG stimulation restrained viability, increased apoptosis, promoted the release of inflammatory cytokines, and affected expressions of hallmarks related to lipid metabolism in HG-treated cells; these changes were partially abolished by CD3D knockdown. Mechanistically, CD3D downregulation ameliorated HG-induced injury in HK-2 cells by blocking the JAK/STAT pathway. This study underscores that CD3D silencing has significant potential as a promising candidate in the treatment of DN.