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MiR-381 negatively regulates cardiomyocyte survival by suppressing Notch signaling

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Abstract

The mechanisms for cardiomyocyte death in cardiovascular diseases are incompletely understood. The aim of this study is to reveal the function of miR-381 in myocardium infarction (MI)-induced cardiomyocyte apoptosis. We established mouse model of MI and cellular models of apoptosis induced by oxidative stress (H2O2 and hypoxia/reoxygenation (H/R)). The expression of miR-381 in these models was assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR); we employed approaches including cell counting kit-8 (CCK-8) assay and flow cytometry to evaluate the cell viability and apoptosis. Notch signaling was determined by western blot analysis of key signaling components including Notch1 intracellular domain (ICD), Jag1, and Hes1. The predicted binding of miR-381 to Jag1 3′ untranslated region (UTR) was validated by luciferase assay. Following MI, miR-381 expression was upregulated time dependently in the border zone of ischemic area but not in the non-ischemic area. MiR-381 expression was also upregulated in cardiomyocytes treated with H2O2 and H/R. Overexpression of miR-381 exacerbated H2O2- and H/R-induced apoptosis of cardiomyocytes; in contrast, inhibition of miR-381 attenuated apoptosis in these conditions. Importantly, in vivo delivery of miR-381 antagomir significantly reduced infarction size. Moreover, miR-381 negatively regulates the cardioprotective Notch signaling in vivo and in vitro, which might be an effect of targeted inhibition of Jag1 by itself. These data indicate an essential role of miR-381/Jag1 pathway in regulating Notch signaling-mediated cardioprotective effect in cardiomyocytes. Our study also provides a potential therapeutic target for cardiovascular diseases.

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Authors and Affiliations

  1. Department of Cardiology and Nephrology, San Ai Tang Hospital, 74 **g-Ning Road, Lanzhou, 730000, China

    Li** Lu, Haicheng Zhang, Weifeng Dong, Wenjia Peng & **g Yang

Authors
  1. Li** Lu
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  2. Haicheng Zhang
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  3. Weifeng Dong
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  4. Wenjia Peng
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  5. **g Yang
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Correspondence to Li** Lu.

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The study was performed in compliance with the guidelines approved by an institute animal care committee.

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The authors declare that they have no conflict of interest.

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Editor: Tetsuji Okamoto

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Lu, L., Zhang, H., Dong, W. et al. MiR-381 negatively regulates cardiomyocyte survival by suppressing Notch signaling. In Vitro Cell.Dev.Biol.-Animal 54, 610–619 (2018). https://doi.org/10.1007/s11626-018-0277-z

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  • DOI: https://doi.org/10.1007/s11626-018-0277-z

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