Interfering with USP50 expression inhibits macrophage pyroptosis in sepsis-induced acute lung injury by degrading NLRP3 protein.

ABSTRACT: Sepsis is a major cause of acute lung injury (ALI) characterized by inflammatory responses. Ubiquitination plays a critical role in the pathogenesis of ALI. This study aimed to investigate the role of USP50, a deubiquitinating enzyme, in sepsis-induced ALI and its underlying molecular mechanisms. THP-1 cells were differentiated into macrophages and exposed to lipopolysaccharide (LPS) to establish an in vitro injury model. Pyroptosis was assessed using immunoblotting, flow cytometry, and enzyme-linked immunosorbent assay. The regulation of USP50 on NLRP3 deubiquitination was analyzed through immunoprecipitation, immunoblotting, and protein stability assays. The in vivo function of USP50 was evaluated using a cecal ligation and puncture (CLP)-induced septic mouse model. Results demonstrated

SUBMITTER: Hu S 

PROVIDER: S-EPMC12287425 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature