Matrix Stiffness Promotes DRP1-Mediated Myofibroblast Senescence to Drive Silica-Induced Pulmonary Fibrosis.

ABSTRACT: Silicosis is an occupational lung disease characterized by diffuse pulmonary fibrosis resulting from inhalation of silica particles. As the disease progresses, lung tissue stiffness continuously increases, driving persistent activation and accumulation of myofibroblasts. However, whether these cells undergo senescence in response to prolonged high matrix stiffness and how such senescence impacts fibrosis progression remain unclear. Here, we established an in vitro model using decellularized lung matrices with varying stiffness to simulate the fibrotic mechanical microenvironment. We found that increased matrix stiffness upregulated mitochondrial fission protein DRP1, inducing excessive mitochondrial fragmentation and accumulation of mitochondrial reactive oxygen species (mtROS), leading to

SUBMITTER: Zeng X 

PROVIDER: S-EPMC12686568 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature