Fibrotic remodelling contributes to heart failure in myocardial infarction.MicroRNAs(miRNAs)play a crucial role in myocardial fibrosis.However,current antifibrotic therapeutic strategies using miRNAs are far from effective.In this study,we aim to investigate the effect of miR-96-5p on cardiac fibrosis.Our work reveals a significant upregulation of miR-96-5p level in the ventricular tissues of myocardial infarction mice,as well as in neonatal rat cardiac fibro-blasts stimulated with TGF-β or Ang Ⅱ as shown by qPCR assay.In myocardial infarction mice,miR-96-5p knock-down using antagomir alleviates the aggravated cardiac fibrosis and exacerbated myocardial function caused by myocardial infarction surgery as shown by the echocardiography and Masson's staining analysis.In contrast,immunofluorescence staining results reveal that miR-96-5p overexpression in neonatal rat cardiac fibroblasts contributes to an increase in the expressions of fibrosis-associated genes and promotes the proliferation and differentiation of cardiac fibroblasts.Conversely,miR-96-5p downregulation using inhibitor presents adverse consequences.Furthermore,Smad7 expression is downregulated in fibrotic cardiac tissues,and the Smad7 gene is identified as a direct target of miR-96-5p by dual luciferase assay.Indeed,Smad7 knockdown weakens the anti-fibrotic effect of the miR-96-5p inhibitor on cardiac fibroblasts.Moreover,Smad3 phosphorylation is elevated in fibrotic cardiac tissues,and interestingly,the Smad3 inhibitor suppresses the profibrotic effect of the miR-96-5p mimic.Taken together,our findings demonstrate that the Smad7/Smad3 signaling pathway mediates the profi-brotic effect of miR-96-5p in cardiac fibrosis.

Huanyu Gu;Yi Duan;Shanshan Li;Qin Wang;Wen Zhen;Wei Zhang;Yingying Zhang;Min Jiang;Chun Wang

Department of Geriatrics,Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School,Nanjing 210008,China;Department of Ophthalmology,Shanghai General Hospital,Shanghai Jiao Tong University,Shanghai 200080,China;School of Basic Medicine and Clinical Pharmacy,China Pharmaceutical University,Nanjing 210009,China

生物化学与生物物理学报（英文版）

[1]Huanyu Gu;Yi Duan;Shanshan Li;Qin Wang;Wen Zhen;Wei Zhang;Yingying Zhang;Min Jiang;Chun Wang-.miR-96-5p regulates myocardial infarction-induced cardiac fibrosis via Smad7/Smad3 pathway)[J].生物化学与生物物理学报（英文版）,2022(12):1874-1888

Fibrotic,remodelling,antifibrotic,profi,brotic

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