TMEM100 attenuates NF-κB activation via disrupting the PRDX1-GNAI2 complex to alleviate acute lung injury

Abstract

Acute lung injury (ALI) is a severe and diffuse inflammatory disorder of interstitial lung. Emerging evidence suggests that TMEM100 is closely associated with lung development and function. However, its role in ALI remains unclear. In this study, we observed a significant downregulation of TMEM100 expression in both mouse lung tissues with ALI and lipopolysaccharide (LPS)-induced pulmonary vascular endothelial cells (PVECs). Overexpression of TMEM100 markedly attenuates LPS-induced lung injury and inflammation, while also restoring the imbalance between proliferation and apoptosis in PVECs. Mechanistically, TMEM100 interacts with both PRDX1 and GNAI2, disrupting the PRDX1-GNAI2 complex and thereby inhibiting LPS-induced NF-{kappa}B activation, which contributes to its anti-inflammatory effects. These findings highlight the protective role of TMEM100 in endotoxin-induced ALI and provide a theoretical basis for understanding its biological functions and potential applications in ALI gene therapy.