Targeting sorting nexin 3 to treat pulmonary fibrosis by dual modulating Wnt/β-catenin signaling.

ABSTRACT: Pulmonary fibrosis (PF) is a chronic progressive lung disorder characterized by overactivation of Wnt/β-catenin signaling and limited therapeutic efficacy. This study identifies sorting nexin 3 (SNX3), a retromer-associated protein, as a dual regulator of PF pathogenesis through coordinated molecular mechanisms. SNX3 is significantly upregulated in PF patients' lungs and bleomycin-induced murine fibrotic models, with predominant localization in alveolar type 2 (AT2) epithelial cells correlating with β-catenin hyperactivation and fibrotic progression. Genetic ablation of SNX3 in AT2 cells attenuated Wnt/β-catenin signaling, collagen deposition, and pulmonary dysfunction, while SNX3 overexpression exacerbated these phenotypes. Mechanistic studies further elucidated two distinct SNX3-driven r

SUBMITTER: Ma D 

PROVIDER: S-EPMC12808692 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature