title: The anti-fibrotic effects of microRNA-153 by targeting TGFBR-2 in pulmonary fibrosis.
abstract: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial fibrotic lung disease with an undefined etiology and no effective treatments. By binding to cell surface receptors, transforming growth factor-β (TGF-β) plays a pivotal role in lung fibrosis. Therefore, the screening of microRNAs (miRNAs), especially those interrupting the effects of TGF-β, may provide information not only on the pathomechanism, but also on the treatment of this disease. In the present study, we found that miR-153 expression was dysregulated in the lungs of mice with experimental pulmonary fibrosis and TGF-β1 decreased miR-153 expression in pulmonary fibroblasts. Moreover, increased miR-153 levels attenuated, whereas the knock down of miR-153 promoted the pro-fibrogenic activity of TGF-β1, and miR-153 reduced the contractile and migratory activities of fibroblasts. In addition, TGFBR2, a transmembrane serine/threonine kinase receptor for TGF-β, was identified as a direct target of miR-153. Furthermore, by post-transcriptional regulation of the expression of TGFBR2, phosphorylation of SMAD2/3 was also influenced by miR-153. These data suggest that miR-153 disturbs TGF-β1 signal transduction and its effects on fibroblast activation, acting as an anti-fibrotic element in the development of pulmonary fibrosis.
authors.affiliation: Department of Geriatrics, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, PR China.
authors.forename: Chunlian
authors.initials: C
authors.lastname: Liang
authors.affiliation: Department of Geriatrics, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, PR China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Geriatrics, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Geriatrics, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, PR China.
authors.forename: Dajiang
authors.initials: D
authors.lastname: Cui
authors.affiliation: Department of Geriatrics, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, PR China. Electronic address: 15209248451@163.com.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Quan
authors.affiliation: Department of Geriatrics, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, PR China.
authors.forename: Weilin
authors.initials: W
authors.lastname: Yang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D001761:Bleomycin / Q000633:toxicity; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000235:genetics* / Q000517:prevention & control; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000903:Antibiotics, Antineoplastic; C577878:MIRN153 microRNA, mouse; D035683:MicroRNAs; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D001761:Bleomycin; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II
keywords: Idiopathic pulmonary fibrosis; TGF-β; TGFBR2; miR-153