Conclusion
BPS treatment increased the binding of YBX1 to the GSK-3β promoter, and GSK-3β protein expression was upregulated, which further caused the upregulation of p-CREB and cAMP, and finally inhibited myocardial fibrosis.
Methods
MI model rats given BPS and cardiac fibroblasts (CFs) treated with BPS and TGF-β. HE staining and Masson staining were used to detect the pathological changes of myocardial tissue. Fibrotic markers were detected by immunohistochemical staining. The expressions of GSK-3β, cAMP response element binding protein (CREB), and p-CREB were analyzed by qPCR and western blot analysis. EDU staining was used to detect the proliferation of CFs. The promoter activity of GSK-3β was detected by luciferase assay. Chromatin immunoprecipitation assay was used to detect the binding levels of GSK-3β promoter and Y-box binding protein 1 (YBX1). The levels of intracellular cyclic adenosine monophosphate (cAMP) were analyzed by enzyme-linked immunosorbent assay (ELISA).
Objective
The aim of this study was to elucidate the mechanism of beraprost sodium (BPS) in the intervention of myocardial fibrosis after myocardial infarction (MI) through glycogen synthase kinase-3β (GSK-3β) and to provide new ideas for intervention in myocardial fibrosis. Materials and
Results
After operation, BPS improved myocardial fibrosis and upregulated GSK-3β protein expression in male SD rats. BPS can down-regulate α-smooth muscle actin (α-SMA) level and up-regulate GSK-3β protein expression in CFs after TGF-β stimulation. Furthermore, GSK-3β knockdown can reverse the effect of BPS on TGF-β-activated CFs, enhance α-SMA expression, and promote the proliferation of CFs. BPS could regulate GSK-3β expression by promoting the binding of GSK-3β promoter to YBX1. BPS induced upregulation of p-CREB and cAMP, resulting in reduced fibrosis, which was reversed by the knockdown of GSK-3β or prostaglandin receptor (IPR) antagonists.