Thioredoxin-interacting protein mediates NALP3 inflammasome activation in podocytes during diabetic nephropathy

被引：88

作者：

Gao, Pan ^{[1
]}

Meng, Xian-Fang ^{[2
]}

Su, Hua ^{[1
]}

He, Fang-Fang ^{[1
]}

Chen, Shan ^{[1
]}

Tang, Hui ^{[1
]}

Tian, Xiu-Juan ^{[1
]}

Fan, Di ^{[1
]}

Wang, Yu-Mei ^{[1
]}

Liu, Jian-She ^{[1
]}

Zhu, Zhong-Hua ^{[1
]}

Zhang, Chun ^{[1
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Nephrol, Wuhan 430022, Peoples R China

[2] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Neurobiol, Wuhan 430030, Peoples R China

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH | 2014年 / 1843卷 / 11期

基金：

中国国家自然科学基金;

关键词：

TXNIP; NALP3; inflammasome; Diabetic nephropathy; Podocyte; UP-REGULATED PROTEIN-1; NLRP3; INFLAMMASOME; OXIDATIVE STRESS; INJURY; HYPERHOMOCYSTEINEMIA; APOPTOSIS; DANGER; BETA; EXPRESSION; CASPASE-1;

D O I：

10.1016/j.bbamcr.2014.07.001

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：

Numerous studies have shown that the NALP3 inflammasome plays an important role in various immune and inflammatory diseases. However, whether the NALP3 inflammasome is involved in the pathogenesis of diabetic nephropathy (DN) is unclear. In our study, we confirmed that high glucose (HG) concentrations induced NALP3 inflammasome activation both in vivo and in vitro. Blocking NALP3 inflammasome activation by NALP3/ASC shRNA and caspase-1 inhibition prevented IL-1 beta production and eventually attenuated podocyte and glomerular injury under HG conditions. We also found that thioredoxin (TRX)-interacting protein (TXNIP), which is a pro-oxidative stress and pro-inflammatory factor, activated NALP3 inflammasome by interacting with NALP3 in HG-exposed podocytes. Knocking down TXNIP impeded NALP3 inflammasome activation and alleviated podocyte injury caused by HG. In summary, the NALP3 inflammasome mediates podocyte and glomerular injury in DN, moreover, TXNIP participates in the formation and activation of the NALP3 inflammasome in podocytes during DN, which represents a novel mechanism of podocyte and glomerular injury under diabetic conditions. (C) 2014 Elsevier B.V. All rights reserved.

引用

页码：2448 / 2460

页数：13

共 42 条

[31] Epithelial-Mesenchymal Transition and Podocyte Loss in Diabetic Kidney Disease [J].