ArticleScientific reports2025
Interfering with USP50 expression inhibits macrophage pyroptosis in sepsis-induced acute lung injury by degrading NLRP3 protein.
Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Cardiomyocyte-enriched OTUD5 alleviates septic cardiomyopathy by promoting NLRP3 deubiquitination and inhibiting NLRP3 inflammasome activation.Clinical and translational medicine · 2026Article
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5 authors.
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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 that USP50 expression was significantly upregulated in the blood of patients with sepsis-induced ARDS and in the lungs of CLP-treated mice. USP50 knockdown suppressed pyroptosis in LPS-stimulated macrophages and septic mice. Furthermore, USP50 inhibition enhanced NLRP3 degradation by facilitating K48-linked ubiquitination. Overexpression of NLRP3 reversed the anti-pyroptotic effects induced by USP50 depletion in macrophages. In conclusion, USP50 suppression attenuates macrophage pyroptosis through inhibition of NLRP3 deubiquitination, thereby reducing lung injury in sepsis-induced models. These findings identify USP50 as a potential therapeutic target for sepsis-associated acute lung injury.
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