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International Journal Of Bilogical Sciences

.: Home > International Journal Of Bilogical Sciences > 2015 > Volume 11 Number 4 > Ning Wang1, Lu-Yao Sun1, Shou-Chen Zhang3, Ran Wei1, Fang Xie1,2, Jing Liu1, Yan Yan1, Ming-Jing Duan1, Lin-Lin Sun1, Ying-Hui Sun1, Hui-Fang Niu1, Rong Zhang1, Jing Ai1

MicroRNA-23a Participates in Estrogen Deficiency Induced Gap Junction Remodeling of Rats by Targeting GJA1

Ning Wang1, Lu-Yao Sun1, Shou-Chen Zhang3, Ran Wei1, Fang Xie1,2, Jing Liu1, Yan Yan1, Ming-Jing Duan1, Lin-Lin Sun1, Ying-Hui Sun1, Hui-Fang Niu1, Rong Zhang1, Jing Ai1
1. Department of Pharmacology, Harbin Medical University (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin, People’s Republic of China, 150081 2. Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, People’s Republic of China, 150081 3. Electron Microscopy Center, Harbin Medical University, Harbin, People’s Republic of China, 150081 Authors with equal contributions to the work. Corresponding authors: Jing Ai: aijing@ems.hrbmu.edu.cn or Ning Wang: wangning@ems.hrbmu.edu.cn. Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, P.R. China 150081; Tel.: +86 451 8667-1354; Fax: +86 451 8667-1354
Abstract :

Increased incidence of arrhythmias in women after menopause has been widely documented, which is considered to be related to estrogen (E2) deficiency induced cardiac electrophysiological abnormalities. However, its molecular mechanism remains incompletely clear. In the present study, we found cardiac conduction blockage in post-menopausal rats. Thereafter, the results showed that cardiac gap junctions were impaired and Connexin43 (Cx43) expression was reduced in the myocardium of post-menopausal rats. The phenomenon was also observed in ovariectomized (OVX) rats, which was attenuated by E2 supplement. Further study displayed that microRNA-23a (miR-23a) level was significantly increased in both post-menopausal and OVX rats, which was reversed by daily E2 treatment after OVX. Importantly, forced overexpression of miR-23a led to gap junction impairment and Cx43 downregulation in cultured cardiomyocytes, which was rescued by suppressing miR-23a by transfection of miR-23a specific inhibitory oligonucleotide (AMO-23a). GJA1 was identified as the target gene of miR-23a by luciferase assay and miRNA-masking antisense ODN (miR-Mask) assay. We also found that E2 supplement could reverse cardiac conduction blockage, Cx43 downregulation, gap junction remodeling and miR-23a upregulation in post-menopausal rats. These findings provide the evidence that miR-23a mediated repression of Cx43 participates in estrogen deficiency induced damages of cardiac gap junction, and highlights a new insight into molecular mechanism of post-menopause related arrhythmia at the microRNA level. 

Keywords :
Connexin43, Post-menopause, Estrogen, MicroRNA-23a, Arrhythmia

Date Deposited : 22 Feb 2016 10:00

Last Modified : 22 Feb 2016 10:00

Official URL: http://www.ijbs.com/v11i4

Volume 11, Number 4, - 2015 , ISSN 1449-2288

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