MicroRNA-23a participates in estrogen deficiency induced gap junction remodeling of rats by targeting GJA1

International Journal of Biological Sciences
Ning WangJing Ai

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, g...Continue Reading

Citations

May 24, 2016·International Journal of Molecular Sciences·Junyi LinZiqin Zhao
Aug 3, 2016·Journal of Molecular and Cellular Cardiology·Heiko LemckeRobert David
Feb 9, 2018·International Journal of Molecular Sciences·Daniel Pérez-CremadesSusana Novella
Sep 22, 2017·Pharmacological Reviews·Luc LeybaertRainer Schulz
Jul 16, 2020·International Journal of Molecular Sciences·Amela Jusic On Behalf Of The Eu-CardioRNA Cost Action
Dec 10, 2016·Frontiers in Physiology·Juan F Calderón, Mauricio A Retamal
Jan 24, 2019·Oxidative Medicine and Cellular Longevity·Daniel Pérez-CremadesSusana Novella
Aug 27, 2019·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Lejla MedzikovicMansoureh Eghbali

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Methods Mentioned

BETA
Infrared Imaging
PCR
transfection
hormone replacement therapy

Software Mentioned

Image
Odyssey
Pro Plus
TargetScan
GraphPad Prism

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