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Targeting Glycogen Synthase Kinase 3 Beta Regulates CD47 Expression After Myocardial Infarction in Rats via the NF-κB
Li-Na Xu1, Shu-Hui Wang1, Xue-Ling Su1
1Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.
Abstract:
The aim of this study was to investigate the effects of the GSK-3β/NF-κB pathway on integrin-associated protein (CD47) expression after myocardial infarction (MI) in rats. An MI Sprague Dawley rat model was established by ligating the left anterior descending coronary artery. The rats were divided into three groups: Sham, MI, and SB + MI (SB216763) groups. Immunohistochemistry was used to observe the changes in cardiac morphology. A significant reduction in the sizes of fibrotic scars was observed in the SB + MI group compared to that in the MI group. SB216763 decreased the mRNA and protein expression of CD47 and NF-κB during MI. Primary rat cardiomyocytes (RCMs) and the H9c2 cell line were used to establish in vitro hypoxia models. Quantitative real-time PCR and western blotting analyses were conducted to detect mRNA and protein expression levels of CD47 and NF-κB and apoptosis-related proteins, respectively. Apoptosis of hypoxic cells was assessed using flow cytometry. SB216763 reduced the protein expression of CD47 and NF-κB in RCMs and H9c2 cells under hypoxic conditions for 12 h, and alleviated hypoxia-induced apoptosis. SN50 (an NF-κB inhibitor) also decreased CD47 protein expression in RCMs and H9c2 cells under hypoxic conditions for 12 h and protected cells from apoptosis. GSK-3β upregulates CD47 expression in cardiac tissues after MI by activating NF-κB, which in turn leads to myocardial cell damage and apoptosis.
Insights
Glycogen synthase kinase 3 beta (GSK-3β) upregulates integrin-associated protein (CD47) after myocardial infarction by activating nuclear factor kappa B (NF-κB), leading to heart cell damage and apoptosis.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Cellular Signaling
Background:
- Myocardial infarction (MI) triggers complex cellular responses, including inflammation and cell death.
- Integrin-associated protein (CD47) and the GSK-3β/NF-κB pathway are implicated in cardiac injury, but their interplay post-MI requires elucidation.
Purpose of the Study:
- To investigate the role of the GSK-3β/NF-κB pathway in regulating CD47 expression following myocardial infarction in a rat model.
- To assess the therapeutic potential of targeting this pathway in mitigating cardiac damage and apoptosis.
Main Methods:
- Establishment of a rat model of myocardial infarction (MI) via coronary artery ligation.
- In vivo analysis using immunohistochemistry to assess cardiac morphology and fibrotic scar size.
- In vitro studies using primary rat cardiomyocytes and H9c2 cells under hypoxic conditions.
- Quantitative real-time PCR and Western blotting to measure mRNA and protein expression of CD47, NF-κB, and apoptosis markers.
- Flow cytometry to evaluate cellular apoptosis.
Main Results:
- SB216763, a GSK-3β inhibitor, significantly reduced fibrotic scar size in MI rats.
- SB216763 treatment decreased both mRNA and protein expression of CD47 and NF-κB in cardiac tissues post-MI.
- In vitro, SB216763 and the NF-κB inhibitor SN50 reduced CD47 expression and alleviated hypoxia-induced apoptosis in cardiomyocytes and H9c2 cells.
- GSK-3β activation of NF-κB was identified as a key mechanism upregulating CD47 expression.
Conclusions:
- The GSK-3β/NF-κB pathway plays a crucial role in upregulating CD47 expression in cardiac tissue after myocardial infarction.
- Inhibition of GSK-3β or NF-κB attenuates CD47 upregulation, reduces myocardial fibrosis, and protects against apoptosis.
- Targeting the GSK-3β/NF-κB/CD47 axis presents a potential therapeutic strategy for managing myocardial infarction complications.
