title: MicroRNA-98 inhibits TGF-β1-induced differentiation and collagen production of cardiac fibroblasts by targeting TGFBR1.
abstract: To investigate the effects of miR-98 on TGF-β1-induced cardiac fibrosis in human cardiac fibroblasts (HCFs), and to establish the mechanism underlying these effects, HCFs were transfected with miR-98 inhibitor or mimic, and then treated with or without TGF-β1. The level of miR-98 was determined by qRT-PCR in TGF-β1-induced HCFs. Cell differentiation and collagen accumulation of HCFs were detected by qRT-PCR and Western blot assays, respectively. The mRNA and protein expressions of TGFBR1 were determined by qRT-PCR and Western blotting. In this study, the outcomes showed that TGF-β1 could dramatically decrease the level of miR-98 in a time- and concentration-dependent manner. Upregulation of miR-98 dramatically improved TGF-β1-induced increases in cell differentiation and collagen accumulation of HCFs. Moreover, bioinformatics analysis predicted that the TGFBR1 was a potential target gene of miR-98. Luciferase reporter assay demonstrated that miR-98 could directly target TGFBR1. Inhibition of TGFBR1 had the similar effect as miR-98 overexpression. Downregulation of TGFBR1 in HCFs transfected with miR-98 inhibitor partially reversed the protective effect of miR-98 overexpression on TGF-β1-induced cardiac fibrosis in HCFs. Upregulation of miR-98 ameliorates TGF-β1-induced differentiation and collagen accumulation of HCFs by downregulation of TGFBR1. These results provide further evidence for protective effect of miR-98 overexpression on TGF-β1-induced cardiac fibrosis.
authors.affiliation: Affiliated Hospital, Medical Department, Hebei University of Engineering, Handan, 056002, Hebei, People's Republic of China. chengranranhebei@yeah.net.|College of Medicine, Hebei University of Engineering, Handan, 056002, Hebei, People's Republic of China. chengranranhebei@yeah.net.
authors.forename: Ranran
authors.initials: R
authors.lastname: Cheng
authors.affiliation: Emergency Department, Affiliated Hospital, Hebei University of Engineering, Congtai Road No. 81, Handan, 056002, Hebei, People's Republic of China.
authors.forename: Ruiying
authors.initials: R
authors.lastname: Dang
authors.affiliation: Affiliated Hospital, Medical Department, Hebei University of Engineering, Handan, 056002, Hebei, People's Republic of China.|College of Medicine, Hebei University of Engineering, Handan, 056002, Hebei, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: College of Medicine, Hebei University of Engineering, Handan, 056002, Hebei, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Ding
authors.affiliation: College of Medicine, Hebei University of Engineering, Handan, 056002, Hebei, People's Republic of China.
authors.forename: Huikun
authors.initials: H
authors.lastname: Hua
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D005355:Fibrosis / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology* / Q000502:physiology; D009206:Myocardium / Q000166:cytology* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C546084:MIRN98 microRNA, human; D035683:MicroRNAs; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D003094:Collagen; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human
keywords: Cardiac fibrosis; Human cardiac fibroblasts; MicroRNA-98; TGF-β1; TGFBR1