CHIP protects against septic acute kidney injury by inhibiting NLRP3-mediated pyroptosis.

ABSTRACT: Septic acute kidney injury (S-AKI), the most common type of acute kidney injury (AKI), is intimately related to pyroptosis and oxidative stress in its pathogenesis. Carboxy-terminus of Hsc70-interacting protein (CHIP), a U-box E3 ligase, modulates oxidative stress by degrading its targeted proteins. The role of CHIP in S-AKI and its relevance with pyroptosis have not been investigated. In this study, we showed that CHIP was downregulated in renal proximal tubular cells in lipopolysaccharide (LPS)-induced S-AKI. Besides, the extent of redox injuries in S-AKI was attenuated by CHIP overexpression or activation but accentuated by CHIP gene disruption. Mechanistically, our work demonstrated that CHIP interacted with and ubiquitinated NLRP3 to promote its proteasomal degradation, leading to the

SUBMITTER: Zhang H 

PROVIDER: S-EPMC10492219 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature