MicroRNA-19b Downregulates Gap Junction Protein Alpha1 and Synergizes with MicroRNA-1 in Viral Myocarditis

International Journal of Molecular Sciences

Junyi Lin¹  Liliang Li¹  Yuhua Li¹  Yiwen Shen¹  Beixu Li¹  Aimin Xue¹  Ziqin Zhao¹  Hongfei Xu²  Ning Sun³  Ruizhen Chen⁴ 

[1] Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China;Department of Forensic Medicine, Soochow University, Suzhou 215123, China;Department of Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China;Key Laboratory of Viral Heart Diseases, Ministry of Public Health, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China;

关键词: viral myocarditis;    microRNA;    gap junction;    miR-19b;    miR-1;   

DOI  :  10.3390/ijms17050741

来源: DOAJ

【 摘 要 】

Viral myocarditis (VMC) is a life-threatening disease that leads to heart failure or cardiac arrhythmia. A large number of researches have revealed that mircroRNAs (miRNAs) participate in the pathological processes of VMC. We previously reported that miR-1 repressed the expression of gap junction protein α1 (GJA1) in VMC. In this study, miR-19b was found to be significantly upregulated using the microarray analysis in a mouse model of VMC, and overexpression of miR-19b led to irregular beating pattern in human cardiomyocytes derived from the induced pluripotent stem cells (hiPSCs-CMs). The upregulation of miR-19b was associated with decreased GJA1 in vivo. Furthermore, a miR-19b inhibitor increased, while its mimics suppressed the expression of GJA1 in HL-1 cells. When GJA1 was overexpressed, the miR-19b mimics-mediated irregular beating was reversed in hiPSCs-CMs. In addition, the effect of miR-19b on GJA1 was enhanced by miR-1 in a dose-dependent manner. These data suggest miR-19b contributes to irregular beating through regulation of GJA1 by cooperating with miR-1. Based on the present and our previous studies, it could be indicated that miR-19b and miR-1 might be critically involved in cardiac arrhythmia associated with VMC.

【 授权许可】

Unknown