miR-145 inhibits isoproterenol-induced cardiomyocyte hypertrophy by targeting the expression and localization of GATA6.

Abstract:

:Excessive βAR stimulation is an independent factor in inducing pathological cardiac hypertrophy. Here, we report miR-145 regulates both expression and localization of GATA6, thereby protecting the heart against cardiomyocyte hypertrophy induced by isoproterenol (ISO). The protective activity of miR-145 was associated with down-regulation of ANF, BNP and β-MHC expression, a decreased rate of protein synthesis, inhibited cardiomyocyte growth and the modulation of several signaling pathways including ERK1/2, JNK and Akt-GSK3β. The anti-hypertrophic effect was abrogated by exogenous over-expression of transcription factor GATA6 which was further identified as a direct target of miR-145. In addition, GSK3β antagonists, LiCl and TDZD8, restored the nuclear accumulation of GATA6, which was attenuated by miR-145 Finally, we observed a dynamic pattern of miR-145 expression in ISO-treated NRCMs and in the hearts of TAC mice. Together, our results identify miR-145 as an important regulator in cardiac hypertrophy.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Li R,Yan G,Zhang Q,Jiang Y,Sun H,Hu Y,Sun J,Xu B

doi

10.1016/j.febslet.2013.04.018

subject

Has Abstract

pub_date

2013-06-19 00:00:00

pages

1754-61

issue

12

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(13)00304-9

journal_volume

587

pub_type

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