mROS-TXNIP axis activates NLRP3 inflammasome to mediate renal injury during ischemic AKI

The International Journal of Biochemistry & Cell Biology
Yi WenBicheng Liu

Abstract

Ischemia/reperfusion (I/R) is a critical risk factor for acute kidney injury (AKI). Recent studies provided evidence that tubular epithelial cells (TEC)-associated inflammation aggravates kidney injury and impairs tissue repair after I/R injury. Here we demonstrated that the Nod-like receptor protein 3 (NLRP3) inflammasome is activated by mitochondrial reactive oxygen species (mROS) during I/R injury via direct interactions between the inflammasome and thioredoxin-interacting protein (TXNIP). Firstly, we found that NLRP3 inflammasome activation was induced by I/R injury, peaking at day 3 after reperfusion. Consistent with this observation, NLRP3 deletion significantly attenuated I/R-induced kidney damage and markers of inflammasome activation. Then, we observed mitochondrial dysfunction, characterized by ultrastructural changes and cytochrome C (Cyt c) redistribution. Mitochondria-targeted antioxidant MitoTEMPO prevented mROS overproduction and the decline in mitochondrial membrane potential (MMP) in vitro. MitoTEMPO treatment also inhibited NLRP3 inflammasome activation and co-localization of NLRP3 and TXNIP after simulated ischemia/reperfusion (SI/R) injury. Finally, we transfected HK-2 cells with TXNIP siRNA to explore the r...Continue Reading

Citations

Nov 13, 2018·The Journal of Pharmacy and Pharmacology·Yu-Si ChengBi-Cheng Liu
Jun 27, 2020·Cancer Biology & Therapy·Chunhua ZhouLulu Zhai
Mar 17, 2020·Frontiers in Cell and Developmental Biology·Huiling XiangJing Xiong
Oct 25, 2020·Biological Trace Element Research·Hongyuan JingMeng-Yao Guo
Feb 12, 2021·International Journal of Molecular Sciences·Alison DominguesValérie Nivet-Antoine
Mar 9, 2019·Free Radical Biology & Medicine·Hong YuRonald J Korthuis
Apr 4, 2021·International Journal of Molecular Sciences·Gonzalo JorqueraPaola Llanos
May 28, 2021·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Xiaohui WangQiang Meng
Jun 6, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Nadire Özenver, Thomas Efferth
Aug 20, 2021·The Journal of International Medical Research·Hai-Peng FanHong Yan

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