Suppression of miR-17 Alleviates Acute Respiratory Distress-associated Lung Fibrosis by Regulating Mfn2

Objective Acute respiratory distress syndrome(ARDS)patients currently have relatively high mortality,which is associated with early lung fibrosis.This study aimed to investigate whether miR-17 suppression could alleviate ARDS-associated lung fibrosis by regulating Mfn2.Methods A mouse model of ARDS-related lung fibrosis was constructed via intratracheal instillation of bleomycin.The expression level of miR-17 in lung tissues was detected via quantitative real time polymerase chain reaction(qRT-PCR).In the ARDS mouse model of lung fibrosis,the mitigating effects of miR-17 interference were evaluated via tail vein injection of the miR negative control or the miR-17 antagomir.The pathological changes in the lung tissue were examined via HE staining and Masson’s trichrome staining,and the underlying molecular mechanism was investigated via ELISA,qRT-PCR and Western blotting.Results Bleomycin-induced pulmonary fibrosis significantly increased collagen deposition and the levels of hydroxyproline(HYP)and miR-17.Interfering with miR-17 significantly reduced the levels of HYP and miR-17 and upregulated the expression of Mfn2.The intravenous injection of the miR-17 antagomir alleviated lung inflammation and reduced collagen deposition.In addition,interference with miR-17 could upregulate LC3B expression,downregulate p62 expression,and improve mitochondrial structure.Conclusion Interfering with miR-17 can improve pulmonary fibrosis in mice by promoting mitochondrial autophagy via Mfn2.