PGC-1 alpha regulates mitochondrial biogenesis to promote silica-induced pulmonary fibrosis.

Abstract

Silicosis is an incurable chronic fibrotic lung disease caused by long-term exposure to respirable silica particles. It is characterized by persistent inflammation and progressive fibrosis of lung tissues, which eventually leads to respiratory failure and seriously affects human health. The high incidence and mortality associated with silicosis have made the disease a widespread public health concern. However, its pathogenesis has not been fully elucidated. Mitochondrial biogenesis plays a crucial role under various fibrotic conditions. However, the mechanism of this process in silicosis is still unclear. Therefore, this study aimed to explore the influence of the PGC-1α gene on mitochondrial biogenesis in the development of silicosis. We established in vivo and in vitro silicosis models by exposing rats and rat type-2 alveolar epithelial cells (RLE-6TN) to silica. Our findings revealed alterations in the mitochondrial structure and function, decreased mitochondrial biogenesis, and reduced expression of mtDNA (Mitochondrial DNA) content. By upregulating the PGC-1α gene in RLE-6TN cells, we activated the PGC-1α- NRF1-TFAM signaling pathway, enhancing mitochondrial biogenesis, increasing citrate synthase and mtDNA content, improving mitochondrial function, and mitigating fibrosis. Our results indicate that the regulation of mitochondrial biogenesis can affect silicosis-induced fibrosis, highlighting the significance of reduced mitochondrial biogenesis in the progression of silicosis-induced fibrosis.