1. MicroRNA-322-5p targeting Smurf2 regulates the TGF-β/Smad pathway to protect cardiac function and inhibit myocardial infarction.
- Author
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Guo L, Li K, Ma Y, Niu H, Li J, Shao X, Li N, Sun Y, and Wang H
- Subjects
- Animals, Rats, Disease Models, Animal, Smad2 Protein metabolism, Smad2 Protein genetics, Gene Expression genetics, Male, Down-Regulation genetics, Rats, Sprague-Dawley, Apoptosis genetics, Smad Proteins metabolism, Glucose metabolism, Smad4 Protein metabolism, Smad4 Protein genetics, Molecular Targeted Therapy, Smad7 Protein metabolism, Smad7 Protein genetics, MicroRNAs genetics, MicroRNAs metabolism, MicroRNAs physiology, Myocardial Infarction genetics, Myocardial Infarction metabolism, Myocardial Infarction pathology, Signal Transduction genetics, Signal Transduction physiology, Ubiquitin-Protein Ligases genetics, Ubiquitin-Protein Ligases metabolism, Ubiquitin-Protein Ligases physiology, Transforming Growth Factor beta metabolism, Myocytes, Cardiac metabolism
- 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., (© 2024. The Author(s) under exclusive licence to Japan Human Cell Society.)
- Published
- 2024
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