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

作　　者：Mei-xia XU Tao XU Ning AN 

机构地区：[1]Department of Critical Care Medicine,Wuhan Fourth Hospital,Wuhan,430033,China [2]Institute of Anesthesiology and Critical Care,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,430022,China

出　　处：《Current Medical Science》2024年第5期964-970,共7页当代医学科学（英文）

基　　金：supported by grants from the Natural Science Foundation of Hubei Province(No.2022CFB423,2023AFB1055);Hubei Province Health and Family Planning Scientific Research Project(No.WJ2023M030).

摘　　要：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.

关 键 词：miR-17 MFN2 acute respiratory distress syndrome pulmonary fibrosis MITOCHONDRIA 

分 类 号：R563.8[医药卫生—呼吸系统]