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Inhibition of miR-143-3p alleviates myocardial ischemia reperfusion injury via limiting mitochondria-mediated apoptosis

  • Chuang-Hong Lu , De-Xin Chen , Kun Dong , Yun-Jiao Wu , Na Na , Hong Wen , Yao-shi Hu , Yuan-Ying Liang , Si-Yi Wu , Bei-You Lin , Feng Huang EMAIL logo and Zhi-Yu Zeng EMAIL logo
Published/Copyright: February 14, 2023
Biological Chemistry
From the journal Biological Chemistry Volume 404 Issue 6

Abstract

MicroRNA (miR)-143-3p is a potential regulatory molecule in myocardial ischemia/reperfusion injury (MI/RI), wherein its expression and pathological effects remains controversial. Thus, a mouse MI/RI and cell hypoxia/reoxygenation (H/R) models were built for clarifying the miR-143-3p’s role in MI/RI. Following myocardial ischemia for 30 min, mice underwent reperfusion for 3, 6, 12 and 24 h. It was found miR-143-3p increased in the ischemic heart tissue over time after reperfusion. Cardiomyocytes transfected with miR-143-3p were more susceptible to apoptosis. Mechanistically, miR-143-3p targeted B cell lymphoma 2 (bcl-2). And miR-143-3p inhibition reduced cardiomyocytes apoptosis upon H/R, whereas it was reversed by a specific bcl-2 inhibitor ABT-737. Of note, miR-143-3p inhibition upregulated bcl-2 with better mitochondrial membrane potential (Δψm), reduced cytoplasmic cytochrome c (cyto-c) and caspase proteins, and minimized infarction area in mice upon I/R. Collectively, inhibition of miR-143-3p might alleviate MI/RI via targeting bcl-2 to limit mitochondria-mediated apoptosis. To our knowledge, this study further clarifies the miR-143-3p’s pathological role in the early stages of MI/RI, and inhibiting miR-143-3p could be an effective treatment for ischemic myocardial disease.

Keywords: apoptosis; B-cell lymphoma-2; microRNA-143-3p; mitochondria; myocardial ischemia reperfusion injury; therapeutic effect
Corresponding authors: Feng Huang and Zhi-Yu Zeng, Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Key Laboratory of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention, Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, No.6 Shuangyong Road, Nanning 530021, Guangxi, China, E-mail: ,
Chuang-Hong Lu, De-Xin Chen and Kun Dong contributed equally to this work.

Funding source: Guangdong Medical Science and technology research fund project

Award Identifier / Grant number: A2022115

Funding source: National Natural Science Foundation of China

Award Identifier / Grant number: 81760057

Award Identifier / Grant number: 82070279

Funding source: Guangxi Key Laboratory of Precision Medicine in Cardio-Cerebrovascular Diseases Control and Prevention

Award Identifier / Grant number: 19-245-34

Funding source: Guangxi Clinical Research Center for Cardio-Cerebrovascular Diseases

Award Identifier / Grant number: AD17129014

  1. Author contributions: CH conceptualized and wrote the manuscript. DX and YJ built in vivo and in vitro models. YS, YY and SY conducted experimental detection. K collected and analyzed data. N, H and BY revised the manuscript. F and ZY conceptualized, revised and supported the manuscript. All of the authors in this study have read and given approval to the submission.

  2. Research funding: This work was supported by the National Natural Science Foundation of China (82070279 and 81760057), Guangxi Key Laboratory of Precision Medicine in Cardio-Cerebrovascular Diseases Control and Prevention (19-245-34), Guangxi Clinical Research Center for Cardio-Cerebrovascular Diseases (AD17129014), Guangdong Medical Science and technology research fund project (A2022115).

  3. Conflict of interest statement: Authors in this study have no potential conflicts of interest.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/hsz-2022-0334).

Received: 2022-11-26
Accepted: 2023-01-13
Published Online: 2023-02-14
Published in Print: 2023-05-25

© 2023 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/hsz-2022-0334
Keywords for this article
apoptosis; B-cell lymphoma-2; microRNA-143-3p; mitochondria; myocardial ischemia reperfusion injury; therapeutic effect

Articles in the same Issue

  1. Frontmatter
  2. Reviews
  3. Unravelling the genetic links between Parkinson’s disease and lung cancer
  4. Small-molecule metabolites in SARS-CoV-2 treatment: a comprehensive review
  5. Research Articles/Short Communications
  6. Molecular Medicine
  7. Dynamic regulation of eEF1A1 acetylation affects colorectal carcinogenesis
  8. New lipophilic organic nitrates: candidates for chronic skin disease therapy
  9. Cell Biology and Signaling
  10. Altered population activity and local tuning heterogeneity in auditory cortex of Cacna2d3-deficient mice
  11. Inhibition of miR-143-3p alleviates myocardial ischemia reperfusion injury via limiting mitochondria-mediated apoptosis
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