title: A novel reciprocal loop between microRNA-21 and TGFβRIII is involved in cardiac fibrosis.
abstract: Cardiac fibrosis is characterized by aberrant proliferation of cardiac fibroblasts and exaggerated deposition of extracellular matrix (ECM) in the myocardial interstitial, and ultimately impairs cardiac function. It is still controversial whether microRNA-21 (miR-21) participates in the process of cardiac fibrosis. Our previous study confirmed that transforming growth factor beta receptor III (TGFβRIII) is a negative regulator of TGF-β pathway. Here, we aimed to decipher the relationship between miR-21 and TGFβRIII in the pathogenic process of myocardial fibrosis. We found that TGF-β1 and miR-21 were up-regulated, whereas TGFβRIII was down-regulated in the border zone of mouse hearts in response to myocardial infarction. After transfection of miR-21 into cardiac fibroblasts, TGFβRIII expression was markedly reduced and collagen content was increased. And, luciferase results confirmed that TGFβRIII was a target of miR-21. It suggests that up-regulation of miR-21 could increase the collagen content and at least in part through inhibiting TGFβRIII. Conversely, we also confirmed that overexpression of TGFβRIII could inhibit the expression of miR-21 and reduce collagen production in fibroblasts. Further studies showed that overexpression of TGFβRIII could also deactivate TGF-β1 pathway by decreasing the expression of TGF-β1 and phosphorylated-Smad3 (p-Smad3). TGF-β1 has been proven as a positive regulator of miR-21. Taken together, we found a novel reciprocal loop between miR-21 and TGFβRIII in cardiac fibrosis caused by myocardial infarction in mice, and targeting this pathway could be a new strategy for the prevention and treatment of myocardial remodeling.
authors.affiliation: Department of Pharmacology, Harbin Medical University, Harbin, Heilongjiang 150081, PR China.
authors.forename: Haihai
authors.initials: H
authors.lastname: Liang
authors.forename: Chun
authors.initials: C
authors.lastname: Zhang
authors.forename: Tao
authors.initials: T
authors.lastname: Ban
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Liu
authors.initials: L
authors.lastname: Mei
authors.forename: Xianmei
authors.initials: X
authors.lastname: Piao
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Lu
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Chu
authors.forename: Baofeng
authors.initials: B
authors.lastname: Yang
mesh_terms: D000818:Animals; D020029:Base Pairing; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005355:Fibrosis; D015870:Gene Expression; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000473:pathology*; D058628:Myofibroblasts / Q000378:metabolism*; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C071736:betaglycan; D048049:Extracellular Signal-Regulated MAP Kinases