SENP1-Sirt3 axis regulates type II alveolar epithelial cell activity to confer resistance against oxidative damage in lung tissue.

ABSTRACT: Oxidative damage exacerbates pulmonary fibrosis by impairing alveolar type II epithelial (AT2) cell function. This study demonstrates that the SUMO-specific protease 1 (SENP1)-Sirtuin 3 (Sirt3) axis, critical for mitochondrial redox regulation, is suppressed in AT2 cells during lung injury. In bleomycin-induced pulmonary fibrosis models, activating the SENP1-Sirt3 axis via Sirt3 SUMOylation site mutation (Sirt3 K223R) reduced Superoxide Dismutase 2 (SOD2) acetylation, thereby lowering mitochondrial reactive oxygen species (mtROS) accumulation and apoptosis. This intervention increased AT2 cell proliferation and differentiation into alveolar type I cells while reducing Keratin 8 (KRT8)⁺ transitional cell number, a profibrotic population. Additionally, SENP1-Sirt3 activation atten

SUBMITTER: Zhang M 

PROVIDER: S-EPMC12274925 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature