Full text

Turn on search term navigation

Copyright Nature Publishing Group Jul 2015

Abstract

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.

Details

Title
RTN1 mediates progression of kidney disease by inducing ER stress
Author
Fan, Ying; Xiao, Wenzhen; Li, Zhengzhe; Li, Xuezhu; Chuang, Peter Y; Jim, Belinda; Zhang, Weijia; Wei, Chengguo; Wang, Niansong; Jia, Weiping; Xiong, Huabao; Lee, Kyung; He, John C
Pages
7841
Publication year
2015
Publication date
Jul 2015
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1700331300
Copyright
Copyright Nature Publishing Group Jul 2015