DsbA-L interacts with VDAC1 in mitochondrion-mediated tubular cell apoptosis and contributes to the progression of acute kidney disease

Li, Xiaozhou1,2; Pan, Jian1,2; Li, Huiling3; Li, Guangdi7; Liu, Bohao1,2; Tang, Xianming1,2; Liu, Xiangfeng6; He, Zhibiao1,2; Peng, Zhenyu1,2; Zhang, Hongliang1,2; Wang, Luxiang1,2; Li, Yijian4; Xiang, Xudong1,2; Chai, Xiangping1,2; Yuan, Yunchang5; Zheng, Peilin8; Zhang, Dongshan1,2

2022-02-01

10.1016/j.ebiom.2022.103859

EBioMedicine   影响因子和分区

2352-3964

["Background we demonstrated that disulfide-bond A oxidoreductase-like protein (DsbA-L) was involved in the progression of renal fibrosis. However, the precise function of DsbA-L in acute kidney injury (AKI), and the mechanisms involved, have yet to be elucidated.","Methods We illustrate the DsbA-L interacted with VDACI by co-IP (co-immunoprecipitation) in vitro and vivo, and found the interaction parts of them by mutation experiment. The above findings were verified by co-localization of them. In addition, we constructed the two model of PT-DsbA-L and VDACI KO mice to verify the function of DsbA-L and VDACI in models of VAN, CLP and I/R-induced AKI.","Findings The PT-DsbA-L-KO mice showed amelioration of I/R, VAN-, and CLP-induced AKI progression via the downregulation of VDACI. Finally, we confirmed these changes in signal molecules by examining in HK-2 cells and kidney biopsies taken from patients with ischemic or acute interstitial nephritis (AIN)-induced AKI. Mechanistically, DsbA-L interacted with amino acids 9-13 and 22-27 of VDACI in the mitochondria of BUMPT cells to induce renal cell apoptosis and mitochondrial injury.","Interpretation This work suggested that DsbA-L, located in the proximal tubular cells, drives the progression of AKI, by directly upregulating the levels of VDACI.Running Title: The role of DsbA-L in AKI Copyright (C) 2022 The Authors. Published by Elsevier B.V."]

DsbA-L VDACI Bax Cyt-c AKI

SCI

英语

其他

General & Internal Medicine ; Research & Experimental Medicine

Medicine, General & Internal ; Medicine, Research & Experimental

WOS:000798068400008

ELSEVIER

Web of Science

1.Dept Emergency Med, Changsha, Hunan, Peoples R China
2.Cent South Univ, Xiangya Hosp 2, Emergency Med & Difficult Dis Inst, Changsha 410011, Hunan, Peoples R China
3.Dept Ophthalmol, Changsha, Hunan, Peoples R China
4.Departmentof Urinary Surg, Changsha, Hunan, Peoples R China
5.Dept Chestsurg, Changsha, Hunan, Peoples R China
6.Second Xiangya Hosp, Dept Gen Surg, Changsha, Hunan, Peoples R China
7.Cent South Univ, Dept Publ Hlth, Changsha, Hunan, Peoples R China
8.Jinan Univ, Affiliated Hosp 1, Southern Univ Sci & Technol, Clin Med Coll 2,Dept Endocrinol,Shenzhen Peoples, Shenzhen, Peoples R China

Li, Xiaozhou,Pan, Jian,Li, Huiling,et al. DsbA-L interacts with VDAC1 in mitochondrion-mediated tubular cell apoptosis and contributes to the progression of acute kidney disease[J]. EBioMedicine,2022,76.

Li, Xiaozhou.,Pan, Jian.,Li, Huiling.,Li, Guangdi.,Liu, Bohao.,...&Zhang, Dongshan.(2022).DsbA-L interacts with VDAC1 in mitochondrion-mediated tubular cell apoptosis and contributes to the progression of acute kidney disease.EBioMedicine,76.

Li, Xiaozhou,et al."DsbA-L interacts with VDAC1 in mitochondrion-mediated tubular cell apoptosis and contributes to the progression of acute kidney disease".EBioMedicine 76(2022).