Chen Jun-Feng, Wu Qi-Shun, Xie Yu-Xian, Si Bo-Lin, Yang Ping-Ping, Wang Wen-Yan, Hua Qin, He Qing
Division of Hemodialysis, Nanjing First Hospital, Nanjing Medical University, Nanjing, China;
Division of Nephrology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China.
FASEB J. 2017 Oct;31(10):4503-4514. doi: 10.1096/fj.201700283R. Epub 2017 Jul 14.
Mitochondrial dysfunction causes renal tubular epithelial cell injury and promotes cell apoptosis and renal tubulointerstitial fibrosis (TIF) progression. TNF receptor-associated protein 1 (TRAP1) is a molecular chaperone protein that is localized in mitochondria. It plays an important role in cell apoptosis; however, its functional mechanism in TIF remains unclear. In this study, we observed the effects of TRAP1 in renal tubular epithelial cell mitochondria in mice with unilateral ureteral obstruction and its function in cell apoptosis and TIF. Results show that TRAP1 could protect the mitochondrial structure in renal tubular epithelial cells; maintain the levels of mitochondrial membrane potential, ATP, and mitochondrial DNA copy number; inhibit reactive oxygen species production; stabilize the expression of the mitochondrial inner membrane protein mitofilin; reduce renal tubular epithelial cell apoptosis; and inhibit TIF. These results provide new theoretical foundations for additional understanding of the antifibrotic mechanism of TRAP1 in the kidney.-Chen, J.-F., Wu, Q.-S., Xie, Y.-X., Si, B.-L., Yang, P.-P., Wang, W.-Y., Hua, Q., He, Q. TRAP1 ameliorates renal tubulointerstitial fibrosis in mice with unilateral ureteral obstruction by protecting renal tubular epithelial cell mitochondria.
线粒体功能障碍会导致肾小管上皮细胞损伤,并促进细胞凋亡以及肾小管间质纤维化(TIF)的进展。肿瘤坏死因子受体相关蛋白1(TRAP1)是一种定位于线粒体的分子伴侣蛋白。它在细胞凋亡中起重要作用;然而,其在TIF中的功能机制仍不清楚。在本研究中,我们观察了TRAP1在单侧输尿管梗阻小鼠肾小管上皮细胞线粒体中的作用及其在细胞凋亡和TIF中的功能。结果表明,TRAP1可以保护肾小管上皮细胞中的线粒体结构;维持线粒体膜电位、ATP和线粒体DNA拷贝数水平;抑制活性氧的产生;稳定线粒体内膜蛋白mitofilin的表达;减少肾小管上皮细胞凋亡;并抑制TIF。这些结果为进一步了解TRAP1在肾脏中的抗纤维化机制提供了新的理论基础。-陈,J.-F.,吴,Q.-S.,谢,Y.-X.,司,B.-L.,杨,P.-P.,王,W.-Y.,华,Q.,何,Q. TRAP1通过保护肾小管上皮细胞线粒体改善单侧输尿管梗阻小鼠的肾小管间质纤维化