The role of a high-salt diet in the modulation of silicosis

Silicosis remains a significant occupational health threat worldwide, affecting millions of workers in various industries. To better understand its underlying mechanisms and identify new intervention targets, the current study explores the pathogenesis of pneumoconiosis. Osteoclast stimulatory transmembrane protein (OC-STAMP) has been found to be an important marker for SiO 2 -induced activation and phenotypic transformation of alveolar type II epithelial cells(ACE2). Moreover, the interaction between OC-STAMP and Moesin is important for regulating epithelial-mesenchymal transition (EMT). Recently, it has been found that a high-salt diet (HSD) may enhance antitumor immune responses and inhibit tumor EMT, achieving antitumor effects. To investigate the role of an HSD in silicosis fibrosis, we intervened with a diet containing 4 % NaCl in a rat model of silicosis to study its effects. The experimental results showed that the HSD slowed the progression of silicosis fibrosis. It was able to downregulate the expression of OC-STAMP, thereby inhibiting the ferroptosis of ACE2, which contributed to the attenuation of lung fibrosis. Furthermore, in in vitro studies, SiO 2 induced ACE2 to produce excessive ROS, Fe 2+ , MDA, and HYP, which could be corrected by a HSD. In a SiO 2 -induced fibrosis model, high salt reverses ferroptosis and the fibrosis phenotype. To explore the underlying mechanisms, we screened for the OC-STAMP potential interacting protein Moesin, which acts together with OC-STAMP to regulate downstream ferroptosis. High salt downregulates OC-STAMP levels to inhibit fibrosis, which is involved in ferroptosis. In conclusion, these results provide evidence that high salt inhibits ferroptosis in epithelial cells and delays lung fibrosis by regulating OC-STAMP/Moesin interactions, offering insights into the pathogenesis of silicosis. • High-salt diet eases the process of fibrosis in silicosis. • High-salt diet alleviates silicosis by attenuating pulmonary ferroptosis. • High-salt diet modulates ACE2 ferroptosis through the OC-STAMP/Moesin axis to alleviate pulmonary fibrosis.