Bazibushen attenuates fibroblast senescence in silica-induced pulmonary fibrosis via FOXO1/PINK1/Parkin Axis

Abstract

Silicosis, an age-related disease, is still a heavy burden on global occupational health. Emerging evidence has revealed that targeting senescent cells may be a promising therapeutic strategy for silicosis. This study was designed to investigate the novel function of Bazibushen (BZBS), a known anti-aging drug, in improving silica-induced lung fibrosis. We first confirmed the accumulation of senescent fibroblasts in the fibrotic regions of silicotic lungs. In both young (6-8 weeks) and aged (12 months) silicotic mice, BZBS exhibited anti-fibrosis and anti-senescence effects. Results of in vitro experiments showed the ability of BZBS to block the expression of p21, fibrotic markers, and senescence-associated secretory phenotype factors. Furthermore, BZBS was observed to attenuate mitochondrial dysfunction in senescent fibroblasts through FOXO1/PINK1/Parkin signaling. Collectively, these results indicated BZBS as a potential anti-fibrosis agent, which exerted its role through maintaining mitochondrial homeostasis in senescent fibroblasts.

Keywords: Bazibushen; Cellular senescence; Fibroblasts; Mitochondrial homeostasis; Silicosis.