TRAP1 ameliorates renal tubulointerstitial fibrosis in mice with unilateral ureteral obstruction by protecting renal tubular epithelial cell mitochondria

被引:26
作者
Chen, Jun-Feng [1 ]
Wu, Qi-Shun [2 ]
Xie, Yu-Xian [3 ]
Si, Bo-Lin [2 ]
Yang, Ping-Ping [2 ]
Wang, Wen-Yan [2 ]
Hua, Qin [2 ]
He, Qing [1 ]
机构
[1] Nanjing Med Univ, Nanjing Hosp 1, Div Hemodialysis, 68 Changle Rd, Nanjing 210006, Jiangsu, Peoples R China
[2] Jiangsu Univ, Affiliated Hosp, Div Nephrol, Zhenjiang, Peoples R China
[3] Jiangsu Univ, Peoples Hosp Suzhou High Tech Dist, Div Nephrol, Suzhou, Peoples R China
基金
中国国家自然科学基金;
关键词
apoptosis; extracellular matrix; mitochondrial DNA; mitofilin; reactive oxygen species; COLORECTAL-CARCINOMA; METABOLIC SWITCH; OXIDATIVE STRESS; CHAPERONE TRAP1; APOPTOSIS; MITOFILIN; INJURY; PROTEIN; OVEREXPRESSION; CARDIOMYOCYTES;
D O I
10.1096/fj.201700283R
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:4503 / 4514
页数:12
相关论文
共 39 条
[1]   TRAP1 Regulates Proliferation, Mitochondrial Function, and Has Prognostic Significance in NSCLC [J].
Agorreta, Jackeline ;
Hu, Jianting ;
Liu, Dongxia ;
Delia, Domenico ;
Turley, Helen ;
Ferguson, David J. P. ;
Iborra, Francisco ;
Pajares, Maria J. ;
Larrayoz, Marta ;
Zudaire, Isabel ;
Pio, Ruben ;
Montuenga, Luis M. ;
Harris, Adrian L. ;
Gatter, Kevin ;
Pezzella, Francesco .
MOLECULAR CANCER RESEARCH, 2014, 12 (05) :660-669
[2]   Profibrotic IHG-1 complexes with renal disease associated HSPA5 and TRAP1 in mitochondria [J].
Bhreathnach, Una ;
Griffin, Brenda ;
Brennan, Eoin ;
Ewart, Leah ;
Higgins, Debra ;
Murphy, Madeline .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2017, 1863 (04) :896-906
[3]   Attenuation of interstitial fibrosis and tubular apoptosis in db/db transgenic mice overexpressing catalase in renal proximal tubular cells [J].
Brezniceanu, Marie-Luise ;
Liu, Fang ;
Wei, Chih-Chang ;
Chenier, Isabelle ;
Godin, Nicolas ;
Zhang, Shao-Ling ;
Filep, Janos G. ;
Ingelfinger, Julie R. ;
Chan, John S. D. .
DIABETES, 2008, 57 (02) :451-459
[4]   Prevention of diabetic nephropathy in Ins2+/-AkitaJ mice by the mitochondria-targeted therapy MitoQ [J].
Chacko, Balu K. ;
Reily, Colin ;
Srivastava, Anup ;
Johnson, Michelle S. ;
Ye, Yaozu ;
Ulasova, Elena ;
Agarwal, Anupam ;
Zinn, Kurt R. ;
Murphy, Michael P. ;
Kalyanaraman, Balaraman ;
Darley-Usmar, Victor .
BIOCHEMICAL JOURNAL, 2010, 432 :9-19
[5]   Targeting TRAP1 as a downstream effector of BRAF cytoprotective pathway: A novel strategy for human BRAF-driven colorectal carcinoma [J].
Condelli, Valentina ;
Maddalena, Francesca ;
Sisinni, Lorenza ;
Lettini, Giacomo ;
Matassa, Danilo Swann ;
Piscazzi, Annamaria ;
Palladino, Giuseppe ;
Amoroso, Maria Rosaria ;
Esposito, Franca ;
Landriscina, Matteo .
ONCOTARGET, 2015, 6 (26) :22298-22309
[6]   Evidence that inhibition of tubular cell apoptosis protects against renal damage and development of fibrosis following ureteric obstruction [J].
Docherty, NG ;
O'Sullivan, OE ;
Healy, DA ;
Fitzpatrick, JM ;
Watson, RWG .
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2006, 290 (01) :F4-F13
[7]   Mitofilin is a transmembrane protein of the inner mitochondrial membrane expressed as two isoforms [J].
Gieffers, C ;
Korioth, F ;
Heimann, P ;
Ungermann, C ;
Frey, J .
EXPERIMENTAL CELL RESEARCH, 1997, 232 (02) :395-399
[8]   Heat shock protein 75 (TRAP1) antagonizes reactive oxygen species generation and protects cells from granzyme M-mediated apoptosis [J].
Hua, Guoqiang ;
Zhang, Qixiang ;
Fan, Zusen .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (28) :20553-20560
[10]   Urine Collagen Fragments and CKD Progression-The Cardiovascular Health Study [J].
Ix, Joachim H. ;
Biggs, Mary L. ;
Mukamal, Kenneth ;
Djousse, Luc ;
Siscovick, David ;
Tracy, Russell ;
Katz, Ronit ;
Delaney, Joseph A. ;
Chaves, Paulo ;
Rifkin, Dena E. ;
Hughes-Austin, Jan M. ;
Garimella, Pranav S. ;
Sarnak, Mark J. ;
Shlipak, Michael G. ;
Kizer, Jorge R. .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2015, 26 (10) :2494-2503