Integrated analyses identify the involvement of microRNA-26a in epithelial-mesenchymal transition during idiopathic pulmonary fibrosis.
Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, and highly lethal fibrotic lung disease with poor treatment and unknown etiology. Emerging evidence suggests that epithelial-mesenchymal transition (EMT) has an important role in repair and scar formation following epithelial injury during pulmonary fibrosis. Although some miRNAs have been shown to be dysregulated in the pathophysiological processes of IPF, limited studies have payed attention on the participation of miRNAs in EMT in lung fibrosis. In our study, we identified and constructed a regulation network of differentially expressed IPF miRNAs and EMT genes. Additionally, we found the downregulation of miR-26a in mice with experimental pulmonary fibrosis. Further studies showed that miR-26a regulated HMGA2, which is a key factor in the process of EMT and had the maximum number of regulating miRNAs in the regulation network. More importantly, inhibition of miR-26a resulted in lung epithelial cells transforming into myofibroblasts in vitro and in vivo, whereas forced expression of miR-26a alleviated TGF-β1- and BLM-induced EMT in A549 cells and in mice, respectively. Taken together, our study deciphered the essential role of miR-26a in the pathogenesis of EMT in pulmonary fibrosis, and suggests that miR-26a may be a potential therapeutic target for IPF.
Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
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Liang
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
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Gu
Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
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Li
Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
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Zhang
Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
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Huangfu
Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
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Hu
Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
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Zhao
Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
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Chen
Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
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Liu
Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
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Dong
Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
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Li
Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
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Lu
Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
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Yang
Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
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Shan
D000818:Animals; D001761:Bleomycin; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D019295:Computational Biology; D030541:Databases, Genetic; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D057809:HEK293 Cells; D025743:HMGA2 Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
D001761:Bleomycin; D003094:Collagen; D025743:HMGA2 Protein; D035683:MicroRNAs; D053773:Transforming Growth Factor beta1; C528163:MIRN26 microRNA, human; C543693:Mirn26 microRNA, mouse