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.

• Authors: Lei Huang, Yang Zhang, Jie Yang, Juan Li, Ju Wu, Faxuan Wang, Yajia Lan, Qin Zhang
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 23 Issue 4 (04 2021) ISSN: 1791-3004 [Electronic] Greece
• PMID: 33649785 (Publication Type: Journal Article)

Chemical References

• Actins
• COL3A1 protein, rat
• Collagen Type I
• Collagen Type I, alpha 1 Chain
• Collagen Type III
• MIRN29 microRNA, rat
• MicroRNAs
• Transforming Growth Factor beta1
• smooth muscle actin, rat

Topics

• Actins (genetics)
• Animals
• Cells, Cultured
• Collagen Type I (genetics)
• Collagen Type I, alpha 1 Chain
• Collagen Type III (genetics)
• Fibroblasts (cytology, metabolism)
• Fibrosis
• Gene Expression Regulation
• Lung (metabolism, pathology)
• Macrophages (cytology, metabolism)
• Male
• MicroRNAs (genetics)
• Pulmonary Fibrosis (genetics)
• Rats, Sprague-Dawley
• Silicosis (genetics)
• Transforming Growth Factor beta1 (genetics)
• Rats