PGC1α inhibits SiO2-induced fibrosis by regulating the mitochondrial respiratory chain.

Silicosis is a fibrotic disease caused by long-term inhalation of SiO2 particles that currently has no effective treatment. Therefore, it is very important to elucidate its pathogenesis and develop novel therapeutic methods. Macrophages are the first line of defense against inhaled dust in the lungs, while mitochondria are critical for regulation of macrophages, thus mitochondrial dysfunction has been shown to play an important role in SiO2-induced pulmonary fibrosis. In this study, we found that PGC1α expression was reduced in SiO2-induced macrophages, mitochondrial respiratory chain was impaired, and fibrosis was enhanced in fibroblasts. In addition, overexpression of PGC1α improved mitochondrial respiratory chain damage and mitigated SiO2-induced fibrosis. Therefore, increasing the expression of PGC1α can inhibit silicosis fibrosis by ameliorating mitochondrial respiratory chain damage. The present study highlight a novel mechanism that PGC1α may participate in SiO2-induced fibrosis by regulating the mitochondrial respiratory chain, suggesting that PGC1α may be an effective therapeutic target for silicosis.