S1PR2通过抑制AKT/GSK-3β减少高糖诱导的内皮增殖

S1PR2 decreasing endothelial cells proliferation induced by high glucose by inhibiting AKT/GSK-3β expression

目的通过下调1-磷酸鞘氨醇2受体(S1PR2),观察其对体外高糖培养的脐静脉内皮细胞增殖的影响并探讨其通路。方法体外培养脐静脉内皮细胞,加入30 mmol/L的D-葡萄糖干预72 h后,检测S1PR2受体变化,内皮增殖情况,通过下调S1PR2后,查看S1PR2影响内皮增殖的可能通路。结果与正常组细胞相比,高糖组内皮细胞存活率降低,S1PR2表达增加,p-AKT/AKT、p-GSK-3β/GSK-3β、β-catenin、cyclin D1表达降低;通过在高糖干预的内皮细胞中加入S1PR2特异性拮抗剂(JTE-013)后,与高糖组相比,内皮细胞存活率增加,p-AKT/AKT、p-GSK-3β/GSK-3β、β-catenin、cyclin D1表达增加,差异均有统计学意义(P<0.05)。结论 S1PR2参与高糖诱导的内皮细胞增殖,其通路可能与AKT/GSK-3β/β-catenin/cyclin D1相关。

Objective To explore the role of S1 PR2 on human umbilical vein endothelial cells(HUVECs) proliferation in high glucose.Methods HUVECs were incubated for 72 hours with stimulation of 5.5 mmol/L glucose(normal glucose control group), or 5.5 mmol/L glucose plus 24.5 mmol/L mannitol(osmotic control group) or 30 mmol/L glucose(high glucose group) or S1 PR2 antagonist(1 μmol/L JTE-013) plus 30 mmol/L glucose(S1 PR2 antagonist group). The cell survival was detected by Cell Counting Kit 8(CCK-8) assay and the expression of proteins was measured by Western blot.Results Compared to the normal glucose control group, the cell survival was significantly decreased in HUVECs under high glucose condition(P<0.05);the expression of S1 PR2 in HUVECs was induced significantly by high glucose(P<0.05);the protein expression of p-Akt, p-GSK-3β,β-catenin, cyclin D1 were significantly decreased in HUVECs under high glucose condition(P<0.05). Compared to the high glucose group, the cell survival was significantly increased(P<0.05);the protein levels of p-Akt, p-GSK-3β,β-catenin, cyclin D1 were significantly increased in the S1 PR2 JTE-013 group(P<0.05).Conclusions S1 PR2 involves in high glucose-induced endothelial cells proliferation by Akt/GSK-3β/β-catenin/cyclin D1.