Na+/H+ exchanger-1 reduces podocyte injury caused by endoplasmic reticulum stress via autophagy activation

被引：18

作者：

Feng, Zhe ^{[1
]}

Tang, Li ^{[1
]}

Wu, Lingling ^{[1
,2
]}

Cui, Shaoyuan ^{[1
]}

Hong, Quan ^{[1
]}

Cai, Guangyan ^{[1
]}

Wu, Di ^{[1
]}

Fu, Bo ^{[1
]}

Wei, Ribao ^{[1
]}

Chen, Xiangmei ^{[1
]}

机构：

[1] Chinese Peoples Liberat Army Gen Hosp, Dept Nephrol, State Key Lab Kidney Dis, Chinese PLA Inst Nephrol & Key Lab, Beijing 100853, Peoples R China

[2] Nankai Univ, Coll Med, Tianjin 300071, Peoples R China

来源：

LABORATORY INVESTIGATION | 2014年 / 94卷 / 04期

基金：

中国国家自然科学基金;

关键词：

autophagy; ER stress; glomerular disease; NHE-1; PHN; podocyte injury; UNFOLDED PROTEIN RESPONSE; CELL-SURVIVAL; NHE1; DIFFERENTIATION; CYTOSKELETON; DEATH;

D O I：

10.1038/labinvest.2014.4

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Podocyte injury has a critical role in the pathogenesis of proteinuria. Induction of endoplasmic reticulum (ER) stress is thought to lead to podocyte injury; however, no effective strategy for reducing ER stress-induced injury has been identified. We investigated specific mechanisms for reducing podocyte injury caused by ER stress. We found that the induction of ER stress in podocytes was related to cytoskeleton injury and increased proteinuria, which was associated with autophagy activation and downregulation of Na+/H+ exchanger-1 (NHE-1) in the rat model of passive Heymann nephritis. Using mouse podocyte cells (MPCs), we showed that ER stress could lead to podocyte injury accompanied by autophagy activation, and the disturbance of autophagy aggravated cytoskeleton loss under conditions of ER stress. The balance between autophagy activation and ER stress was critical to podocyte survival, in which the efficiency of autophagy could have a pivotal role. Strikingly, the overexpression and small interfering RNA knockdown of NHE-1 results suggested that NHE-1 exerts a protective effect by reducing the loss of synaptopodin in MPCs exposed to ER stress. This protective mechanism involves NHE-1 activation of autophagy via the PI3K/Akt pathway to reduce ER stress injury in podocytes. This mechanism may provide a new pathway to prevent podocyte injury.

引用

页码：439 / 454

页数：16

共 41 条

[1] MAP-LC3, a promising autophagosomal marker, is processed during the differentiation and recovery of podocytes from PAN nephrosis [J].