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MiR-137-3p exacerbates the ischemia-reperfusion injured cardiomyocyte apoptosis by targeting KLF15

Naunyn-Schmiedeberg's Archives of Pharmacology volume 393, pages 1013–1024 (2020)Cite this article

Abstract

Ischemia-reperfusion (I/R) injury is a kind of the tissue damage caused by an abrupt re-supplying tissue with blood after a period of ischemia or hypoxia. It contributes to a wide range of pathological processes including kidney injury, circulatory arrest, and especially cardiovascular disease. However, the underlying pathological mechanism is not fully elucidated. Previously, extensive studies demonstrated that miRNAs participate in the pathogenesis of I/R injury, such as I/R-induced cardiomyocyte apoptosis. Here, we found that miR-137-3p, a mature form of miR-137, was up-regulated in I/R-injured cardiomyocytes of myocardial infarction patients. Deficiency of miR-137-3p partly alleviated the cardiomyocyte apoptosis and oxidative stress induced by hypoxia-reoxygenation (H/R) treatment in H9c2 cells. Also, we provided evidences that miR-137-3p directly targeted the 3’ UTR of KLF15 mRNA to down-regulate its expression, and loss function of KLF15 significantly abolished the deleterious effects of ectopic miR-137-3p on cardiomyocytes both in vitro and in vivo. Collectively, these observations highlight a molecular perturbation in the pathogenesis of I/R injury in cardiomyocytes.

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Funding

This research was supported by Changzhi Medical College Doctoral Startup Fund (BS201908) and Science and technology innovation project of shanxi higher education (2019L0673).

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Author notes

  1. Tingting Zhao and Zhi Qiu contributed equally to this work.

Affiliations

  1. Department of Cardiology, Peace hospital attached to Changzhi, Changzhi, 046000, Shanxi, People’s Republic of China

    Tingting Zhao, Zhi Qiu & Yonghua Gao

  2. Department of Cardiology, The Xiangya Hospital of central south university, Changsha, 410000, Hunan, People’s Republic of China

    Yonghua Gao

  3. Department of Clinical Laboratory, Affiliated Hospital of Xuzhou Medical University, 89 Huaihai Road, Xuzhou, 221000, Jiangsu, People’s Republic of China

    Yonghua Gao

Authors
  1. Tingting Zhao
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  2. Zhi Qiu
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  3. Yonghua Gao
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Contributions

R.H. and T.Z conceived and designed the research. Tingting Zhao and R.Q conducted experiments. R.H. contributed new reagents or analytical tools. Tingting Zhao and R.Q analyzed data. R.H. wrote the manuscript. All authors read and approved the manuscript.

Corresponding author

Correspondence to Yonghua Gao.

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The authors declare that they have no conflict of interest.

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Appendix

Appendix

Table 1 General information of myocardial infraction patients
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Zhao, T., Qiu, Z. & Gao, Y. MiR-137-3p exacerbates the ischemia-reperfusion injured cardiomyocyte apoptosis by targeting KLF15. Naunyn-Schmiedeberg's Arch Pharmacol 393, 1013–1024 (2020). https://doi.org/10.1007/s00210-019-01728-w

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  • DOI: https://doi.org/10.1007/s00210-019-01728-w

Keywords

  • Ischemia-reperfusion (I/R) injury
  • Hypoxia-reoxygenation (H/R) injury
  • miR-137-3p
  • I/R-induced apoptosis
  • KLF15