首页|微RNA-372-3p负调控FBXO11参与心肌成纤维细胞活化的机制

微RNA-372-3p负调控FBXO11参与心肌成纤维细胞活化的机制

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目的 探讨在心肌成纤维细胞(CFs)活化过程中,微RNA(miRNA)对FBXO11表达的调控及其分子机制.方法 正常心肌成纤维细胞(hCFs)经miR-372-3p mimics转染和转化生长因子β1(TGF-β1)诱导后,采用qRT-PCR检测FBXO11及hCFs活化标志物的表达;通过双荧光素酶报告基因实验检测FBXO11与miR-372-3p的结合情况.结果 hCFs活化后,FBXO11表达呈剂量依赖性上调,且与hCFs活化标志物表达水平呈正相关.敲除FBXO11后,hCFs活化标志物表达下调.在hCFs体外纤维化诱导模型中,miR-372-3p表达下调,且与FBXO11呈显著负相关.miR-372-3p通过与FBXO11 3'非翻译区(3'UTR)的特定位点结合,对FBXO11进行转录后调控.过表达miR-372-3p可以抑制TGF-β1诱导的FBXO11高表达和hCFs活化标志物表达水平升高.结论 miR-372-3p通过负调控FBXO11表达参与hCFs活化.
miR-372-3p Anti-fibroblast Activation by Targeting FBXO11 in Transforming Growth Factor-β1-Induced Human Cardiac Fibroblasts
Objective To investigate the mechanism of FBXO11 expression regulated by microRNA(miRNA)and its molecular mechanism in the activating process of cardiac fibroblasts.Methods Human normal cardiac fibroblasts(hCFs)were transfected with miR-372-3p mimics and induced by transforming growth factor-β1(TGF-β1),and qRT-PCR was used to detect FBXO11 as well as the expression of hCFs activation markers;the binding of FBXO11 to MiR-372-3p was detected by dual luciferase reporter gene assay.Results Upon hCFs activation,the expression of FBXO11 was upregulated in dose-dependent manner and positively correlated with the activation markers of hCFs.After the knockdown of FBXO11,the expression of activation markers of hCFs was downregulated.In vitro,in a TGF-β1-induced fibrosis model of hCFs,MiR-372-3p expression was down-regulated and significantly negatively correlated with FBXO11.MiR-372-3p was up-regulated in an in TGF-β1-induced fibrosis model of hCFs by binding to the FBXO11 3'untranslated region(3'UTR).Overexpression of miR-372-3p inhibited TGF-β1-induced high FBXO11 expression and elevated levels of hCFs activation markers.Conclusion miR-372-3p is involved in the anti-hCFs activation by negatively regulating FBXO11 expression.

FBXO11miR-372-3pCardiac fibroblastsTransforming growth factor-β1

柯晓、易明、陈俊羽、郑欣馨、徐延路

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中国医学科学院阜外医院深圳医院心血管内科,广东深圳 518057

湖南中医药大学附属第二中西医结合医院心血管内科,长沙 410300

中国医学科学院 北京协和医学院 国家心血管病中心 阜外医院心血管内科,北京 100037

FBXO11 微RNA-372-3p 心肌成纤维细胞 转化生长因子β1

广东省基础与应用基础研究基金面上项目深圳市科技计划项目湖南省自然科学基金

2021A1515010178JCYJ202103241246050152024JJ9572

2024

中国分子心脏病学杂志
中国医学科学院,中国协和医学院

中国分子心脏病学杂志

CSTPCD
影响因子:0.426
ISSN:1671-6272
年,卷(期):2024.24(3)
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