title: Thioredoxin-Interacting Protein Mediates NLRP3 Inflammasome Activation Involved in the Susceptibility to Ischemic Acute Kidney Injury in Diabetes.
abstract: Kidney in diabetic state is more sensitive to ischemic acute kidney injury (AKI). However, the underlying mechanisms remain unclear. Herein, we examined the impact of diabetes mellitus on thioredoxin-interacting protein (TXNIP) expression and whether mediated NLRP3 activation was associated with renal ischemia/reperfusion- (I/R-) induced AKI. In anin vivomodel, streptozotocin-induced diabetic rats showed higher susceptibility to I/R injury with increased TXNIP expression, which was significantly attenuated by resveratrol (RES) treatment (10 mg/kg intraperitoneal daily injection for 7 consecutive days prior to I/R induction). RES treatment significantly inhibited TXNIP binding to NLRP3 in diabetic rats subjected to renal I/R injury. Furthermore, RES treatment significantly reduced cleaved caspase-1 expression and production of IL-1βand IL-18. In anin vitrostudy using cultured human kidney proximal tubular cell (HK-2 cells) in high glucose condition (HG, 30 mM) subjected to hypoxia/reoxygenation (H/R), HG combined H/R (HH/R) stimulated TXNIP expression which was accompanied by increased NLRP3 expression, ROS generation, caspase-1 activity and IL-1βlevels, and aggravated HK-2 cells apoptosis. All these changes were significantly attenuated by TXNIP RNAi and RES treatment. In conclusion, our results demonstrate that TXNIP-mediated NLRP3 activation through oxidative stress is a key signaling mechanism in the susceptibility to AKI in diabetic models.
authors.affiliation: Department of Anesthesiology, Renmin Hospital of Wuhan University, 99 Zi Yang Road, Wuhan, Hubei 430060, China.
authors.forename: Ye Da
authors.identifier: 0000-0001-7340-6990
authors.initials: YD
authors.lastname: Xiao
authors.affiliation: Department of Anesthesiology, Renmin Hospital of Wuhan University, 99 Zi Yang Road, Wuhan, Hubei 430060, China.
authors.forename: Ya Yi
authors.initials: YY
authors.lastname: Huang
authors.affiliation: Department of Anesthesiology, Renmin Hospital of Wuhan University, 99 Zi Yang Road, Wuhan, Hubei 430060, China.
authors.forename: Hua Xin
authors.initials: HX
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Renmin Hospital of Wuhan University, 99 Zi Yang Road, Wuhan, Hubei 430060, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology, Renmin Hospital of Wuhan University, 99 Zi Yang Road, Wuhan, Hubei 430060, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Leng
authors.affiliation: Department of Anesthesiology, Renmin Hospital of Wuhan University, 99 Zi Yang Road, Wuhan, Hubei 430060, China.
authors.forename: Min
authors.identifier: 0000-0001-8103-3397
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Renmin Hospital of Wuhan University, 99 Zi Yang Road, Wuhan, Hubei 430060, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, Renmin Hospital of Wuhan University, 99 Zi Yang Road, Wuhan, Hubei 430060, China.
authors.forename: Zhong-Yuan
authors.identifier: 0000-0002-5807-9554
authors.initials: ZY
authors.lastname: Xia
mesh_terms: D058186:Acute Kidney Injury / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000276:immunology* / Q000378:metabolism; D018797:Cell Cycle Proteins; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D058847:Inflammasomes / Q000276:immunology; D008297:Male; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D012307:Risk Factors; D015398:Signal Transduction; D014162:Transfection
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C573346:Nlrp3 protein, rat; C486715:TXNIP protein, human; C493796:TXNIP protein, rat