RTN1 mediates progression of kidney disease by inducing ER stress

被引：87

作者：

Fan, Ying ^{[1
,2
]}

Xiao, Wenzhen ^{[1
,2
]}

Li, Zhengzhe ^{[1
]}

Li, Xuezhu ^{[1
]}

Chuang, Peter Y. ^{[1
]}

Jim, Belinda ^{[3
]}

Zhang, Weijia ^{[1
]}

Wei, Chengguo ^{[1
]}

Wang, Niansong ^{[2
]}

Jia, Weiping ^{[2
]}

Xiong, Huabao ^{[4
]}

Lee, Kyung ^{[1
]}

He, John C. ^{[1
]}

机构：

[1] Icahn Sch Med Mt Sinai, Div Nephrol, Dept Med, New York, NY 10029 USA

[2] Shanghai Jiao Tong Univ, Dept Nephrol, Affiliated Peoples Hosp 6, Shanghai 200233, Peoples R China

[3] Albert Einstein Coll Med, Div Nephrol, Dept Med, Jacobi Med Ctr, Bronx, NY 10467 USA

[4] Icahn Sch Med Mt Sinai, Inst Immunol, Dept Med, New York, NY 10029 USA

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

关键词：

ENDOPLASMIC-RETICULUM-STRESS; NEURODEGENERATIVE DISEASES; DIABETIC-NEPHROPATHY; INSULIN-RESISTANCE; INHIBITION; PROTEIN; MICE; APOPTOSIS; CELLS; ACTIVATION;

D O I：

10.1038/ncomms8841

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Identification of new biomarkers and drug targets for chronic kidney disease (CKD) is required for the development of more effective therapy. Here we report an association between expression of reticulon 1 (RTN1) and severity of CKD. An isoform-specific increase in the expression of RTN1A is detected in the diseased kidneys from mice and humans, and correlates inversely with renal function in patients with diabetic nephropathy. RTN1 overexpression in renal cells induces ER stress and apoptosis, whereas RTN1 knockdown attenuates tunicamycin-induced and hyperglycaemia-induced ER stress and apoptosis. RTN1A interacts with PERK through its N-terminal and C-terminal domains, and mutation of these domains prevents this effect on ER stress. Knockdown of Rtn1a expression in vivo attenuates ER stress and renal fibrosis in mice with unilateral ureteral obstruction, and also attenuates ER stress, proteinuria, glomerular hypertrophy and mesangial expansion in diabetic mice. Together, these data indicate that RTN1A contributes to progression of kidney disease by inducing ER stress.

引用

页数：16

共 44 条

[1]

No Nogo66-and NgR-Mediated Inhibition of Regenerating Axons in the Zebrafish Optic Nerve [J].