前列腺素E2通过环磷酸腺苷-蛋白激酶A信号通路上调人THP-1巨噬细胞血管内皮生成因子表达并促进体外血管生成

Prostaglandin E2 (PGE2) upregulates vascular endothelial growth factor(VEGF) expressions in THP-1 derived macrophages via c AMP/PKA signaling pathway and promotes in vitro angiogenesis

目的探讨前列腺素E2(prostaglandin E2,PGE2)是否上调人THP-1巨噬细胞血管内皮生长因子(vascular endothelial growth factor,VEGF)表达及其促进体外血管生成的分子机制。方法用不同浓度PGE2、2种PGE2受体(EP2和EP4)拮抗剂或环磷酸腺苷-蛋白激酶A(c AMP-PKA)通路特异性抑制剂SQ22536、H89处理人THP-1巨噬细胞,Western blotting检测人THP-1巨噬细胞内VEGF蛋白表达的变化,Transwell小室和Matrigel胶实验分析PGE2对人THP-1巨噬细胞促进人脐静脉血管内皮细胞(HUVECs)迁移和成管的影响。结果 PGE2通过EP2受体激活c AMP-PKA通路,上调人THP-1巨噬细胞VEGF蛋白表达,以及促进HUVECs的迁移和成管效应。结论 PGE2可能通过上调人THP-1源巨噬细胞VEGF的表达,并且促进血管生成,对胚胎着床起保护作用。

ObjectiveTo explore the possible molecular mechanism of prostaglandin E2 （PGE2） in regulating vascular endothelial growth factor （VEGF） expression in THP-1 macrophages. To analyze whether the media from PGE2- treated THP-1 derived macrophages improves angiogenesis of human umbilical vein endothelial cells （HUVECs） in vitro. MethodsTHP-1 derived macrophages were treated with PGE2, and PGE2 combined with EP2 receptor antagonist AH6809, EP4 receptor antagonist AH23848, adenylate cyclase inhibitor SQ22536 and PKA inhibitor H89 respectively. Western blotting was used to examine the protein level of VEGF in THP-1 macrophages. Conditioned supernatants were obtained to stimulate HUVECs, migration and tube formation ability of the HUVECs were assessed. ResultsPGE2 upregulated the expression of VEGF in THP-1 derived macrophages through EP2 receptor and cAMP-PKA signaling pathway, and induced migration and accelerated the growth of tube like structures of HUVECs. ConclusionPGE2 may play a protective role in embryo implantation by promoting VEGF synthesis and improving angiogenesis.