Surfactant protein A deficiency aggravates silica-induced pulmonary fibrosis by promoting intrinsic apoptosis of alveolar type II epithelial cells

BACKGROUND: Silicosis is an incurable occupational lung disease characterized by progressive fibrosis and respiratory failure, imposing a significant global health burden. Surfactant protein A (SP-A) plays a critical role in maintaining pulmonary homeostasis, yet its mechanistic role in silicosis remains unclear. METHODS: ) mice were generated to evaluate the functional role of SP-A in vivo, including lung pathology, collagen deposition, and pulmonary function. RNA sequencing was performed to uncover underlying molecular mechanisms. A549 cells with SP-A silenced by siRNA were employed for in vitro experiments. RESULTS: mice showed markedly exacerbated silica-induced pulmonary fibrosis, extracellular matrix deposition, and functional decline. RNA-seq analysis highlighted activation of intrinsic apoptosis pathways related to pulmonary fibrosis. Mechanistically, SP-A deficiency disrupted the balance of Bcl-2 and Bax, activated Caspase-3, and promoted epithelial apoptosis. Inhibition of the intrinsic apoptosis pathway mitigated the pro-apoptotic effects of SP-A silencing. CONCLUSIONS: These findings demonstrate that SP-A deficiency exacerbates silica-induced pulmonary fibrosis by promoting epithelial apoptosis involving the Bcl-2/Bax/Caspase pathway, highlighting the role of SP-A in fibrogenesis progression and providing a basis for its potential therapeutic target for silicosis.