MiR-23a Is Involved in Myocardial Ischemia/Reperfusion Injury by Directly Targeting CX43 and Regulating Mitophagy
Abstract
Activation of CX43 signaling protects myocardial cells from myocardial ischemia/reperfusion (I/R) injury. However, the underlying mechanism remains unclear. MicroRNAs (miRNAs) are well known to play important roles in the progression of diverse diseases. Here, we first confirmed the expression profile of CX43 in rat heart tissues with I/R injury. Then, microRNAs (miRNAs) that target CX43 were predicted using miRDB, miRWalk, and TargetScan. The candidate miR-23a was selected, and its expression level in I/R samples was investigated. To determine the role of miR-23a, rat primary myocardial cells were transfected with miR-23a mimics after they were subjected to hypoxia-reoxygenation (H/R) injury. Transfection of miR-23a mimics stimulated mitophagy through the PINK1/Parkin pathway and downregulated the protein level of CX43. Treatment of miR-23a-transfected cells with NF-kB inhibitors completely abolished miR-23a-mediated mitophagy after H/R. Moreover, miR-23a transfection significantly suppressed CX43 expression and enhanced mitophagy in the model heart in vivo. Therefore, miR-23a plays a detrimental role in myocardial I/R injury by enhancing mitophagy and inhibiting CX43 mRNA.
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In models of cardiac dysfunction, miR-23 can regulate cell metabolism and reduce injury through directly targeting GLS to restore glutamine metabolism and regulating CX43 to modulate mitochondrial autophagy.
“In models of cardiac dysfunction, researchers have revealed that miR-23 can regulate cell metabolism and reduce injury through two pathways: directly targeting GLS to restore glutamine metabolism and regulating CX43 to modulate mitochondrial autophagy [53,54].”
From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [54]
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References 39 · Cited by 26
- Authors
- Wang, L., Li, Q., Diao, J., Lin, L., & Wei, J.
- Affiliations
- Second Affiliated Hospital of Xi'an Jiaotong University (CN)
- Corresponding author
- Wei, Jin
- Venue
- Inflammation
- Published
- 2021-03-02
- Volume
- 44
- Issue
- 4
- Pages
- 1581-1591
- ISSN
- 0360-3997 (ISSN-L)
- 1573-2576
- OpenAlex
- W3135018491
- Cited by
- 26
- References
- 39
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 6 · 2023: 5 · 2022: 7 · 2021: 2
- FWCI
- 3.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Inflammation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- miR-23a, myocardial ischemia-reperfusion injury, connexin 43, mitophagy, PINK1/Parkin pathway, NF-κB signaling, hypoxia/reoxygenation injury, microRNA target regulation, cardioprotection
- MeSH terms
- Animals, Cells, Cultured, Male, Myocardial Reperfusion Injury, Rats, Sprague-Dawley, Connexin 43, MicroRNAs, Rats, Mitophagy
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