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.
miR‐145 inhibits isoproterenol‐induced cardiomyocyte hypertrophy by targeting the expression and localization of GATA6
Ruotian Li,G. Yan,Qun Zhang,Yue Jiang,Haixiang Sun,Yali Hu,Jianxin Sun,Biao Xu
Published 2013 in FEBS Letters
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- Publication year
2013
- Venue
FEBS Letters
- Publication date
2013-06-19
- Fields of study
Biology, Medicine
- Identifiers
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- Source metadata
Semantic Scholar, PubMed
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