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- Title
The extracellular signal-regulated kinase 1/2 triggers angiogenesis in human ectopic endometrial implants by inducing angioblast differentiation and proliferation.
- Authors
Arlier, Sefa; Murk, William; Guzeloglu‐Kayisli, Ozlem; Semerci, Nihan; Larsen, Kellie; Tabak, Mehmet S.; Arici, Aydin; Schatz, Frederick; Lockwood, Charles J.; Kayisli, Umit A.
- 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.
- Subjects
NEOVASCULARIZATION; EXTRACELLULAR signal-regulated kinases; CELL proliferation; ENDOMETRIUM physiology; CD34 antigen; VASCULAR endothelial growth factors; PHOSPHORYLATION; CELL differentiation
- Publication
American Journal of Reproductive Immunology, 2017, Vol 78, Issue 6, pn/a
- ISSN
1046-7408
- Publication type
Article
- DOI
10.1111/aji.12760