title: MicroRNA-9 inhibits high glucose-induced proliferation, differentiation and collagen accumulation of cardiac fibroblasts by down-regulation of TGFBR2.
abstract: To investigate the effects of miR-9 on high glucose (HG)-induced cardiac fibrosis in human cardiac fibroblasts (HCFs), and to establish the mechanism underlying these effects. HCFs were transfected with miR-9 inhibitor or mimic, and then treated with normal or HG. Cell viability and proliferation were detected by using the Cell Counting Kit-8 (CCK-8) assay and Brdu-ELISA assay. Cell differentiation and collagen accumulation of HCFs were detected by qRT-PCR and Western blot assays respectively. The mRNA and protein expressions of transforming growth factor-β receptor type II (TGFBR2) were determined by qRT-PCR and Western blotting. Up-regulation of miR-9 dramatically improved HG-induced increases in cell proliferation, differentiation and collagen accumulation of HCFs. Moreover, bioinformatics analysis predicted that the TGFBR2 was a potential target gene of miR-9 Luciferase reporter assay demonstrated that miR-9 could directly target TGFBR2. Inhibition of TGFBR2 had the similar effect as miR-9 overexpression. Down-regulation of TGFBR2 in HCFs transfected with miR-9 inhibitor partially reversed the protective effect of miR-9 overexpression on HG-induced cardiac fibrosis in HCFs. Up-regulation of miR-9 ameliorates HG-induced proliferation, differentiation and collagen accumulation of HCFs by down-regulation of TGFBR2. These results provide further evidence for protective effect of miR-9 overexpression on HG-induced cardiac fibrosis.
authors.affiliation: Vasculocardiology Department, The Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Li
authors.affiliation: Vasculocardiology Department, The Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Yingnan
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Vasculocardiology Department, The Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Zhendong
authors.initials: Z
authors.lastname: Su
authors.affiliation: Vasculocardiology Department, The Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, China weiguoqianharbin@sina.com.
authors.forename: Guoqian
authors.initials: G
authors.lastname: Wei
mesh_terms: D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism*; D005355:Fibrosis / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D014162:Transfection / Q000379:methods; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
chemical_list: C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D003094:Collagen; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D005947:Glucose
keywords: TGFBR2; cardiac fibrosis; high glucose; human cardiac fibroblasts; miRNA-9