Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease. In recent years, alveolar epithelial cell-derived exosomes (AEc-Exos) have been shown to influence the progression of pulmonary fibrosis. The main objective of this study was to investigate the specific molecular mechanism of the effect of AEc-Exos on IPF. In this study, a cell fibrosis model was constructed using TGF-β, and a mouse fibrosis model was constructed with bleomycin (BLM), treated with AEc-Exos, which was interfered with by treatment with a miR-450b-5p inhibitor. Experimental analysis revealed that AEc-Exos activated autophagy by inhibiting the expression of HDAC7 and attenuated TGF-β-induced pulmonary fibrosis and that inhibiting miR-450b-5p weakened the therapeutic effect of AEc-Exos. starBase analysis revealed that HDAC7 was the target gene of miR-450b-5p, and experiments revealed that overexpression of HDAC7 weakened the therapeutic effect of AEc-Exos on TGF-β-induced pulmonary fibrosis. In in vivo experiments, BLM induced pulmonary fibrosis and inhibited autophagy in mice, an effect that was weakened after the addition of AEc-Exos, which partially reversed the effect of BLM after further inhibition of miR-450b-5p. In summary, this study revealed that AEc-Exos significantly inhibited the development of pulmonary fibrosis by activating autophagy through the miR-450b-5p/HDAC7 molecular axis, which provides new ideas for the clinical treatment of pulmonary fibrosis.