MicroRNA-98 inhibits TGF-β1-induced differentiation and collagen production of cardiac fibroblasts by targeting TGFBR1

被引:38
作者
Cheng, Ranran [1 ,3 ]
Dang, Ruiying [2 ]
Zhou, Yan [1 ,3 ]
Ding, Min [3 ]
Hua, Huikun [3 ]
机构
[1] Hebei Univ Engn, Med Dept, Affiliated Hosp, Handan 056002, Hebei, Peoples R China
[2] Hebei Univ Engn, Affiliated Hosp, Emergency Dept, Congtai Rd 81, Handan 056002, Hebei, Peoples R China
[3] Hebei Univ Engn, Coll Med, Handan 056002, Hebei, Peoples R China
关键词
MicroRNA-98; Human cardiac fibroblasts; TGF-beta; 1; Cardiac fibrosis; TGFBR1; GROWTH-FACTOR-BETA; FIBROSIS; ANGIOTENSIN; PROLIFERATION; MECHANISMS; EXERCISE; PATHWAY; MIR-21; AKT;
D O I
10.1007/s13577-017-0163-0
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
To investigate the effects of miR-98 on TGF-beta 1-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-beta 1. The level of miR-98 was determined by qRT-PCR in TGF-beta 1-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-beta 1 could dramatically decrease the level of miR-98 in a time- and concentration-dependent manner. Upregulation of miR-98 dramatically improved TGF-beta 1-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-beta 1-induced cardiac fibrosis in HCFs. Upregulation of miR-98 ameliorates TGF-beta 1-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-beta 1-induced cardiac fibrosis.
引用
收藏
页码:192 / 200
页数:9
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