Intervention Effects of Up-regulating miR-133 on Myocardial Fibrosis and TGF-β1/Smad3 Pathway in Rats with Chronic Heart Failure
YANG Hui
ZHONG Jianghua
MA Tianyi
AO Xue
SUN Dingjun
Abstract：Objective:To investigate the effect of up-regulating microRNA-133(miR-133)on myocardial fibrosis and transforming growth factor-β1(TGF-β1)/receptor activation type 3(Smad3)pathway in rats with chronic heart failure.Methods:The fifty specific pathogen free(SPF)Wistar rats were selected,10 rats were randomly selected as the control group,and the other 40 rats were modeled.A total of 30 rats were successfully modeled.A total of 30 modeling rats were randomly divided into model group,miR-133 inhibitor group,and miR-133 analog group,with 10 rats in each group.The rats in control group and model group were intraperitoneally injected with normal saline,the rats in miR-133 inhibitor group were intraperitoneally injected with miR-133 inhibitor,and the rats in miR-133 mimic group were injected with miR-133 mimic.Real-time fluorescence quantitative method was used to detecte the expression levels of miR-133,TGF-β1 mRNA and Smad3 mRNA in each group.The ejection fraction(EF)and shortening fraction(FS),the left ventricular end-diastolic diameter(LVEDD),and left ventricular end-systolic diameter(LVESD)levels were measured by ultrasonography.Myocardial interstitial collagen area,visual field myocardial tissue area,perivascular collagen area and vascular lumen area were measured by computer image analysis system.Myocardial collagen volume fraction(CVF)and ratio of perivascular collagen area to vascular lumen area(PVCA/LA)were calculated.The protein expressions of TGF-β1 and Smad3 pathways were detected by Western Blot.Results:Compared with the control group,the expression of miR-133,EF,and FS decreased in the model group,miR-133 inhibitor group,and miR-133 mimics group,while LVEDD,LVESD,CVF,PVCA/LA,TGF-β1 mRNA,Smad3 mRNA,and TGF-β1/Smad3 signaling pathway protein were increased.There were statistically significant differences(P＜0.05).Compared with the model group,the expression of miR-133,EF and FS in the miR-133 inhibitor group and the miR-133 mimic group increased,while LVEDD,LVESD,CVF,PVCA/LA,TGF-β1 mRNA,Smad3 mRNA,and TGF-β1/Smad3 signaling pathway protein decreased.There were statistically significant differences(P＜0.05).Compared with the miR-133 inhibitor group,the expression of miR-133,EF,and FS in the miR-133 inhibitor group and the miR-133 mimic group increased,while LVEDD,LVESD,CVF,PVCA/LA,TGF-β1 mRNA,Smad3 mRNA,and TGF-β1/Smad3 signaling pathway protein decreased.There were statistically significant differences(P＜0.05).Conclusion:Upregulation of miR-133 expression could alleviate cardiac injury in rats with chronic heart failure,and the mechanism might be related to inhibition of TGF-β1/Smad3 signaling pathway.
Keywords：chronic heart failuremicroRNA-133transforming growth factor-β1/receptor-activated type 3 signaling pathwaymyocardial fibrosis soluble stromal lysin 2ratsexperimental study
Publication Date：2025-05-25
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：5( 1494-1498 )