miR-146b-5p Suppresses Btg2 to Promote Fibroblast Proliferation and Is Associated with Prrx2 and Myh10

Abstract

Pulmonary fibrosis is a chronic progressive lung disease characterized by abnormal proliferation and activation of fibroblasts. However, the regulatory mechanisms of miRNAs and their target genes on fibroblast proliferation during silicosis (silica-induced pulmonary fibrosis) remain incompletely understood. A mouse silicosis model was established by dynamic dust inhalation, and lung tissues were collected at 7, 14, 28, and 56 days after dust exposure, followed by multi-time-point miRNA sequencing and transcriptome sequencing. Using integrated omics, bioinformatics analysis, and molecular interaction validation, the key miRNAs and their target genes regulating fibroblast proliferation were screened and verified. The results showed that time-series clustering and H&E staining confirmed successful modeling of the transition from acute inflammation to chronic fibrosis induced by SiO2. Differentially expressed miR-146b-5p during SiO2 stress may affect the cell cycle of fibroblasts by regulating Btg2. Mechanistically, IP-MS combined with Co-IP identified interactions between Btg2 and Prrx2 or Myh10, suggesting their potential involvement in this regulatory process. These findings provide new experimental evidence for the molecular mechanisms of silica-induced pulmonary fibrosis in a mouse model, and may offer insights for understanding the pathogenesis of human silicosis.