Prostaglandin E receptor 3 promotes the dysfunction of vascular smooth muscle cells induced by platelet-derived growth factor via regulating PI3K/Akt pathway

BACKGROUND AND OBJECTIVE: The dysfunction of vascular smooth muscle cells (VSMCs) contributes to the pathogenesis of atherosclerosis, which is associated with coronary heart disease and acute myocardial infarction (AMI). This study is conducted to explain the biological function of prostaglandin E receptor 3 (EP3) in regulating the phenotypes of VSMCs. MATERIALS AND METHODS: Platelet-derived growth factor-BB (PDGF-BB) was used to treat VSMCs to construct the cell model. qPCR was performed to examine the expression of EP3 in the VSMCs after PDGF-BB treatment. After EP3 was silenced, inhibited or overexpressed in VSMCs, CCK-8 assay, BrdU assay, flow cytometry and Transwell assay were performed to detect the viability, proliferation, cell cycle progression and migration of VSMCs. In addition, the expression levels of PI3K, p-p85, Akt, p-Akt in VSMCs was measured by Western blotting. RESULTS: The expression of EP3 in VSMCs is promoted by PDGF-BB treatment in a time- and dose-dependent manner. EP3 overexpression facilitates the viability, proliferation and migration of VSMCs while silencing EP3 or pharmacological inhibition of EP3 represses the dysfunction of VSMCs induced by PDGF-BB. EP3 promoted phosphorylation of p85, Akt (Ser473) and Akt (Thr308) in VSMCs, and the promoting effects of EP3 on the viability, proliferation, migration and cell cycle progression of VSMCs were counteracted after PI3K signalling was inhibited. CONCLUSION: EP3 participates in inducing the dysfunction of VSMCs induced by PDGF via regulating PI3K/Akt pathway, suggesting EP3 is a therapeutic target for atherosclerosis, AMI and other cardiovascular diseases.

Automated summary

This study investigated the biological function of EP3 in regulating the phenotypes of VSMCs. The results showed that EP3 promoted the viability, proliferation, and migration of VSMCs, and participated in the dysfunction induced by PDGF through regulating the PI3K/Akt pathway. These findings suggest that EP3 may serve as a therapeutic target for atherosclerosis, AMI, and other cardiovascular diseases.