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Updated: May 20, 2025
Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury
Published on: March 7, 2022
Exploring miR-3148's impact on Krüppel-like factor 6-driven mitophagy and apoptosis in myocardial ischemic injury
Chusheng Huang1, Lipeng Li1, Hailong Deng1
1Department of Thoracic and Cardiovascular Surgery, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China.
Objective:
Myocardial infarction (MI) is a leading cause of death worldwide, accounting for millions of fatalities annually. The injury and repair of cardiomyocytes are closely associated with the changes in gene expression. MicroRNAs could serve as a potential target for MI treatment. This work aims to investigate the role of miR-3148 in mitochondrial dynamics during acute MI (AMI) with a specific focus on its regulatory mechanisms in mitophagy and apoptosis, which could reveal potential therapeutic targets for AMI treatment.
Material And Methods:
MiR-3148 levels in patients with AMI and experimental models were measured to assess the effects of miR-3148 on cardiomyocyte viability under oxygen and glucose deprivation (OGD). The present investigation involved monitoring mitophagy markers, including PTEN-induced kinase 1 (PINK1), parkin RBR E3 ubiquitin-protein ligase (Parkin), Beclin1, and microtubule-associated protein 1A/1B light chain 3 II/I (LC3 II/I) ratio, as well as apoptotic markers such as cysteine-aspartic acid protease (Caspase) 9, Caspase 3, and cytochrome C (Cyt C). In addition, Krüppel-like factor 6 (KLF6) was examined as a target of miR-3148.
Results:
MiR-3148 was significantly elevated in patients with AMI and models. MiR-3148 overexpression reduced cardiomyocyte viability, whereas miR-3148 knockdown protected against OGD injury. The inhibition of miR-3148 activated mitophagy, as shown by the increased PINK1, Parkin, Beclin1 levels, and LC3 II/I ratios, and reduced sequestosome 1 (p62), and apoptotic markers levels. MiR-3148 directly targeted KLF6, reducing its expression. The suppression of KLF6 aggravated OGD injury by disrupting PINK1/Parkin-mediated mitophagy and enhancing apoptosis. Attenuating KLF6 expression reversed the protective effects of miR-3148 inhibition, indicating reciprocal regulation.
Conclusion:
In myocardial ischemic injury, miR-3148 modulates PINK1/Parkin-mediated mitophagy and apoptosis through KLF6 regulation. This finding highlights miR-3148 as a key factor in the pathogenesis of AMI and as a potential therapeutic target.
Insights
MicroRNA-3148 (miR-3148) exacerbates acute myocardial infarction (AMI) by inhibiting mitophagy and promoting apoptosis. Targeting miR-3148 or its downstream effects offers a potential therapeutic strategy for AMI treatment.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Cellular Stress Response
Background:
- Myocardial infarction (MI) is a major global cause of mortality.
- MicroRNAs (miRNAs) play critical roles in cardiomyocyte injury and repair.
- Understanding miRNA involvement in acute MI (AMI) is crucial for developing new therapies.
Purpose of the Study:
- To investigate the role of miR-3148 in mitochondrial dynamics during AMI.
- To elucidate the regulatory mechanisms of miR-3148 in mitophagy and apoptosis.
- To identify potential therapeutic targets for AMI treatment.
Main Methods:
- Measured miR-3148 levels in AMI patients and experimental models.
- Assessed cardiomyocyte viability under oxygen and glucose deprivation (OGD).
- Monitored mitophagy markers (PINK1, Parkin, Beclin1, LC3 II/I) and apoptosis markers (Caspase 9, Caspase 3, Cyt C).
- Examined Krüppel-like factor 6 (KLF6) as a direct target of miR-3148.
Main Results:
- miR-3148 levels were significantly elevated in AMI.
- miR-3148 overexpression reduced cardiomyocyte viability; knockdown protected against OGD injury.
- miR-3148 inhibition activated mitophagy and reduced apoptosis, partly via KLF6 regulation.
- KLF6 suppression aggravated OGD injury by disrupting mitophagy and enhancing apoptosis.
Conclusions:
- miR-3148 modulates mitophagy and apoptosis via KLF6 regulation in myocardial ischemic injury.
- miR-3148 is a key factor in AMI pathogenesis.
- miR-3148 represents a potential therapeutic target for AMI.
