MiR-146a-Modified Lung Fibroblast Attenuates Transforming Growth Factor Beta-Induced Fibrosis Progress via Downregulation of Early Growth Response Factor 1

Abstract

This study investigated the role of miR-146a in lung fibrosis, specifically focusing on idiopathic pulmonary fibrosis (IPF), which is characterized by excessive alveolar fibrosis and collagen synthesis. The study aimed to explore the impact and mechanism of miR-146a on lung fibrosis using in vitro methods. Human lung fibroblasts (LFs) were transfected with miR-146a mimics and inhibitors to examine their effects. Transforming growth factor-β (TGF-β) was used to activate LFs for 24 hours, while phosphate-buffered saline (PBS)-treated cells served as the control group. The transfection efficiency, level of LFs activation, collagen expression, and cell viability were investigated. The results demonstrated that administration of miR-146a mimics attenuated LFs activation and reduced collagen levels by inhibiting the expression of EGR1, an important factor involved in cell proliferation and differentiation that is positively associated with fibrogenesis. On the other hand, miR-146a inhibitor increased EGR1 expression, but did not significantly affect LFs activation and collagen expression. Furthermore, rescuing EGR1 expression reversed the decrease in LFs activation and collagen expression induced by increased levels of miR-146a. These findings indicate that miR-146a overexpression has an anti-fibrotic effect on LFs by inhibiting EGR1 expression, thereby restraining cell activation and reducing collagen deposition. Therefore, miR-146a holds promise as a potential therapeutic target for mitigating lung fibrosis diseases.