Anti-fibrotic effects and the mechanism of action of miR-29c in silicosis

Abstract

Despite increasing evidence suggesting a role for the miR-29 family in the suppression of fibrosis, its role in silicosis remains unknown. The present study aimed to examine the anti-fibrotic effects and specific mechanism of action of microRNA (miR)-29c in pulmonary silicosis using animal and cell models. miR-29c expression levels were examined in the lungs of silicotic rats via reveres transcription-quantitative (RT-q)PCR. A Transwell system employing co-cultures of pulmonary fibroblasts and macrophages was used to establish an in vitro cell model of silicosis, and lentivirus was used to overexpress or knockdown miR-29c in cultured cells. Changes in collagen type I α I (COL1α1), COL3α1, α-smooth muscle actin (α-SMA) and TGF-β1 expression levels were determined via RT-qPCR and western blotting. Data analysis was performed using R software. miR-29c expression was significantly downregulated in the lungs of silicotic rats and in the pulmonary fibroblasts of the in vitro model of silicosis. Furthermore, COL1α1, COL3α1, α-SMA and TGF-β1 expression levels were significantly increased in cultured fibroblasts following 12 or 18 h exposure to SiO2. Lentiviral-mediated knockdown of miR-29c resulted in increased the expression levels of COL1α1, COL3α1, α-SMA and TGF-β1, while lentiviral-mediated miR-29c overexpression significantly suppressed the expression levels of these fibrosis-related genes. Taken together, these results demonstrated that miR-29c was significantly associated with silica-induced pulmonary fibrosis and the expression levels of COL1α1, COL3α1, TGF-β1 and α-SMA are under the regulation of miR-29c to different extents. This study therefore identified possible candidate molecular targets for preventing or delaying the occurrence and progression of silicosis.