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MicroRNA-322-5p targeting Smurf2 regulates the TGF-β/Smad pathway to protect cardiac function and inhibit myocardial infarction

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Abstract

Acute coronary artery blockage leads to acute myocardial infarction (AMI). Cardiomyocytes are terminally differentiated cells that rarely divide. Treatments preventing cardiomyocyte loss during AMI have a high therapeutic benefit. Accumulating evidence shows that microRNAs (miRNAs) may play an essential role in cardiovascular diseases. This study aims to explore the biological function and underlying regulatory molecular mechanism of miR-322-5p on myocardial infarction (MI). This study's miR-322-5p is downregulated in MI-injured hearts according to integrative bioinformatics and experimental analyses. In the MI rat model, miR-322-5p overexpression partially eliminated MI-induced changes in myocardial enzymes and oxidative stress markers, improved MI-caused impairment on cardiac functions, inhibited myocardial apoptosis, attenuated MI-caused alterations in TGF-β, p-Smad2, p-Smad4, and Smad7 protein levels. In oxygen–glucose deprivation (OGD)-injured H9c2 cells, miR-322-5p overexpression partially rescued OGD-inhibited cell viability and attenuated OGD-caused alterations in the TGF-β/Smad signaling. miR-322-5p directly targeted Smurf2 and inhibited Smurf2 expression. In OGD-injured H9c2 cells, Smurf2 knockdown exerted similar effects to miR-322-5p overexpression upon cell viability and TGF-β/Smad signaling; moreover, Smurf2 knockdown partially attenuated miR-322-5p inhibition effects on OGD-injured H9c2 cells. In conclusion, miR-322-5p is downregulated in MI rat heart and OGD-stimulated rat cardiomyocytes; the miR-322-5p/Smurf2 axis improves OGD-inhibited cardiomyocyte cell viability and MI-induced cardiac injuries and dysfunction through the TGF-β/Smad signaling.

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Funding

This study was supported by the Scientific Research Incentive Fund of Shanxi Cardiovascular Hospital (no. XYS20180206) and the Shanxi Provincial Health Commission “Four Batch Science and Technology Innovation Project of Medical Development" (no. 2021XM45).

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Authors and Affiliations

  1. Department of Cardiology, Shanxi Cardiovascular Hospital, Taiyuan, 030000, Shanxi, China

    Liping Guo, Huaiming Niu, Jun Li, Xin Shao, Na Li, Yuehui Sun & Haixiong Wang

  2. Department of Cardiology, The People’s Hospital of Suzhou, Suzhou New District, Suzhou, 215129, Jiangsu, China

    Ke Li

  3. Department of General Practice, Taiyuan Central Hospital, Taiyuan, 030000, Shanxi, China

    Yan Ma

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  1. Liping Guo
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  2. Ke Li
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  7. Na Li
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Correspondence to Haixiong Wang.

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All the animal experimental procedures were approved by the Ethics Committee of Shanxi Cardiovascular Hospital (approval number: NO20200509).

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Guo, L., Li, K., Ma, Y. et al. MicroRNA-322-5p targeting Smurf2 regulates the TGF-β/Smad pathway to protect cardiac function and inhibit myocardial infarction. Human Cell (2024). https://doi.org/10.1007/s13577-024-01062-1

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