title: Thioredoxin-interacting protein mediates NALP3 inflammasome activation in podocytes during diabetic nephropathy.
abstract: 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-1β 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.
authors.affiliation: Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Gao
authors.affiliation: Department of Neurobiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Xian-Fang
authors.initials: XF
authors.lastname: Meng
authors.affiliation: Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Su
authors.affiliation: Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: He
authors.affiliation: Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Xiu-Juan
authors.initials: XJ
authors.lastname: Tian
authors.affiliation: Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Di
authors.initials: D
authors.lastname: Fan
authors.affiliation: Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Jian-She
authors.initials: JS
authors.lastname: Liu
authors.affiliation: Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Zhong-Hua
authors.initials: ZH
authors.lastname: Zhu
authors.affiliation: Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: drzhangchun@hust.edu.cn.
authors.forename: Chun
authors.initials: C
authors.lastname: Zhang
keywords: Diabetic nephropathy; NALP3 inflammasome; Podocyte; TXNIP