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MiR-124 Regulates the Inflammation and Apoptosis in Myocardial Infarction Rats by Targeting STAT3
Xiao-Jing Cheng1, Lei Li1, Ben-Qiang Xin2
1Department of Cardiovascular Medicine, Rizhao People's Hospital, No. 126, Taian Road, Donggang District, Rizhao, 276800, Shandong, China.
Abstract:
This study aimed to discover the effect of miR-124/STAT3 axis on the inflammation and cell apoptosis in myocardial infarction (MI) rats. Sprague-Dawley (SD) male rats were selected for establishing MI models and divided into Sham, MI, MI + anti-miR-124 and MI + Ad-miR-124 groups. Cardiac function was detected via echocardiography. Hematoxylin & eosin (HE) and triphenyltetrazolium chloride (TTC) staining were used to observe the pathological changes and infarction area, while transferase (TdT)-mediated D-UTP-biotin nick end labeling (TUNEL) assay was to observe myocardial apoptosis. Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum levels of inflammatory cytokines. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting were performed to determine the mRNA and protein levels, respectively. Dual luciferase reporter gene assay revealed that STAT3 was a target gene of miR-124. The expression levels of miR-124 were increased and the pSTAT3/STAT3 ratio was reduced in the MI rats. The rats in the MI group showed enhanced LVEDD and LVESD, reduced LVEF and LVFS, as well as larger myocardial infarction area compared with the Sham group, Besides, IL-1β, IL-6, TNF-α and MCP-1 levels were elevated and the expressions of Bax/Bcl-2 ratio and cleaved caspase-3 were downregulated in MI group. We further found that silencing miR-124 improved cardiac function, reduced infarction area and the levels of inflammatory cytokines, as well as prevented myocardial apoptosis in MI rats. Silencing miR-124 could inhibit the inflammation and apoptosis of myocardial cells, thereby relieving the MI injury via upregulation of STAT3.
Insights
MicroRNA-124 (miR-124) exacerbates myocardial infarction (MI) injury by promoting inflammation and apoptosis. Silencing miR-124 protects against MI by upregulating STAT3, reducing inflammation and cell death.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Biochemistry
Background:
- Myocardial infarction (MI) is a leading cause of mortality, characterized by inflammation and cardiomyocyte apoptosis.
- The role of microRNAs, specifically miR-124, and their downstream targets like STAT3 in MI pathogenesis requires further elucidation.
Purpose of the Study:
- To investigate the impact of the miR-124/STAT3 axis on inflammation and apoptosis in a rat model of myocardial infarction.
- To determine the therapeutic potential of modulating miR-124 levels in mitigating MI-induced damage.
Main Methods:
- Myocardial infarction models were established in Sprague-Dawley rats, divided into Sham, MI, MI + anti-miR-124, and MI + Ad-miR-124 groups.
- Cardiac function was assessed using echocardiography; pathological changes and apoptosis were evaluated via HE, TTC, and TUNEL assays.
- Inflammatory cytokine levels were measured by ELISA, and gene/protein expression was analyzed using qRT-PCR and Western blotting. A dual luciferase reporter assay confirmed STAT3 as a miR-124 target.
Main Results:
- MI rats exhibited impaired cardiac function, increased infarct size, elevated inflammatory cytokines (IL-1β, IL-6, TNF-α, MCP-1), and increased myocardial apoptosis (higher Bax/Bcl-2 ratio, cleaved caspase-3).
- miR-124 expression was upregulated, and the pSTAT3/STAT3 ratio was reduced in MI rats, indicating STAT3 is negatively regulated by miR-124.
- Silencing miR-124 significantly improved cardiac function, reduced infarct size, decreased inflammation, and inhibited apoptosis in MI rats, correlating with STAT3 upregulation.
Conclusions:
- The miR-124/STAT3 axis plays a critical role in mediating inflammation and apoptosis following myocardial infarction.
- Inhibition of miR-124 demonstrates a protective effect against MI injury by upregulating STAT3, thereby suppressing myocardial inflammation and apoptosis.
