Influence of LncRNA OIP5-AS1 on chronic heart failure with myocardial fibrosis studied based on microRNA-216a-5p/Smad7 axis

Tao Jinsong; Zhang Ting; Li Weizhang; Lu Yichao; Seidu A.Richard; Gu Jian; Li Jian; Han Jin

doi:10.3969/j.issn.1674-4055.2025.09.13

Abstract：Objective To investigate the influence of LncRNA OIP5-AS1 on chronic heart failure(CHF)with myocardial fibrosis based on micro RNA-216a-5p(miR-216a-5p)/Smad7 axis.Methods The model of CHF mouse was established by using transverse aortic constriction(TAC).The effect of lncRNA OIP5-AS1 in myocardial fibrosis in vivo was studied.The myocardial fibrosis in vitro was simulated through angiotensinⅡ(AngⅡ)affecting cardiac fibroblasts(CFs).The expressions of lncRNA OIP5-AS1 in CFs were detected by using real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)and Western blotting assay.LncRNA OIP5-AS1 overexpression plasmid was transfected to validate the effect of lncRNA OIP5-AS1 overexpression on myocardial fibrosis in vitro.Additionally,miR-216a-5p was predicted as a downstream target of lncRNA OIP5-AS1,and Smad7 was a downstream target of miR-216a-5p by using bioinformatics analysis.The levels of lncRNA OIP5-AS1 and miR-216a-5p in serum samples were detected by using qRT-PCR.Results The expression of LncRNA OIP5-AS1 was significantly downregulated in AngⅡ treated CFs in heart tissue of CHF mice(P＜0.001).The upregulated lncRNA OIP5-AS1 expression inhibited significantly fibrotic phenotype in CFs induced by AngⅡ(P＜0.001).The overexpression of lncRNA OIP5-AS1 in CFs reversed CFs proliferation induced by AngⅡ(P＜0.01).After overexpression of lncRNA OIP5-AS1 in CFs,miR-216a-5p expression was significantly downregulated(P＜0.001).Furthermore,in CFs transfected with miR-216a-5p mimic,both mRNA and protein expressions of Smad7 were significantly reduced(P＜0.001).Conclusion LncRNA OIP5-AS1 may inhibit myocardial fibrosis through miR-216a-5p/Smad7 axis,which provides a new target for treating CHF myocardial fibrosis.