The extracellular signal-regulated kinase 1/2 triggers angiogenesis in human ectopic endometrial implants by inducing angioblast differentiation and proliferation

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Extracellular signal-regulated kinase 1/2 activation in human endometrial endothelial cells promotes ectopic endometrial angiogenesis by inducing angioblast differentiation and proliferation.

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Abstract

PROBLEM: The role of extracellular signal-regulated kinase (ERK)1/2-mediated angiogenesis during endometriotic nidation is unknown. We posit that ERK1/2-induced angioblast differentiation and proliferation promotes ectopic endometrial angiogenesis. METHODS OF STUDY: Human eutopic and ectopic endometria were immunostained for total- (T-) or phosphorylated- (P-) ERK1/2 or double-immunostained for P-ERK1/2-CD34 and PCNA-CD34. Estradiol (E2 ), cytokines, normal peritoneal fluid (NPF) or endometriotic peritoneal fluid (EPF) ±PD98059, an ERK1/2 inhibitor, treaded primary human endometrial endothelial cells (HEECs) were evaluated by T-/P-ERK1/2 immunoblotting, MTT viability and tube formation assays. RESULTS: HEECs exhibited higher endothelial P-ERK1/2 immunoreactivity in ectopic vs eutopic endometria. Double-immunostained ectopic endometria displayed abundant CD34-positive angioblasts exhibiting strong P-ERK1/2 and PCNA immunoreactivity. EPF and vascular growth factor (VEGF)-A significantly increased HEEC proliferation and P-ERK1/2 levels. PD98059 reduced basal, EPF, and VEGF-induced HEEC proliferation and promoted vascular stabilization following tube formation. CONCLUSION: Enhanced ERK1/2 activity in angioblasts by such peritoneal factors as VEGF, E2 induces proliferation to trigger ectopic endometrial angiogenesis.

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Condition tags

endometriosis

MeSH descriptors

Choristoma Endometriosis Endometrium Endothelial Cells Extracellular Signal-Regulated MAP Kinases Neovascularization, Pathologic Neovascularization, Pathologic Cell Differentiation Cell Differentiation Cell Proliferation Cell Proliferation Cells, Cultured Cells, Cultured Choristoma Choristoma Endometriosis Endometriosis Endometrium Endometrium Endothelial Cells

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