The extracellular signal-regulated kinase 1/2 triggers angiogenesis in human ectopic endometrial implants by inducing angioblast differentiation and proliferation
Sefa Arlier
Department of Obstetrics & Gynecology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA
Search for more papers by this authorWilliam Murk
Department of Obstetrics, Gynecology & Reproductive Sciences, School of Medicine, Yale University, New Haven, CT, USA
Search for more papers by this authorOzlem Guzeloglu-Kayisli
Department of Obstetrics & Gynecology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA
Search for more papers by this authorNihan Semerci
Department of Obstetrics & Gynecology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA
Search for more papers by this authorKellie Larsen
Department of Obstetrics & Gynecology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA
Search for more papers by this authorMehmet S. Tabak
Department of Obstetrics, Gynecology & Reproductive Sciences, School of Medicine, Yale University, New Haven, CT, USA
Search for more papers by this authorAydin Arici
Department of Obstetrics, Gynecology & Reproductive Sciences, School of Medicine, Yale University, New Haven, CT, USA
Search for more papers by this authorFrederick Schatz
Department of Obstetrics & Gynecology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA
Search for more papers by this authorCharles J. Lockwood
Department of Obstetrics & Gynecology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA
Search for more papers by this authorCorresponding Author
Umit A. Kayisli
Department of Obstetrics & Gynecology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA
Correspondence
Umit A. Kayisli, Department of Obstetrics & Gynecology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Email: [email protected]
Search for more papers by this authorSefa Arlier
Department of Obstetrics & Gynecology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA
Search for more papers by this authorWilliam Murk
Department of Obstetrics, Gynecology & Reproductive Sciences, School of Medicine, Yale University, New Haven, CT, USA
Search for more papers by this authorOzlem Guzeloglu-Kayisli
Department of Obstetrics & Gynecology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA
Search for more papers by this authorNihan Semerci
Department of Obstetrics & Gynecology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA
Search for more papers by this authorKellie Larsen
Department of Obstetrics & Gynecology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA
Search for more papers by this authorMehmet S. Tabak
Department of Obstetrics, Gynecology & Reproductive Sciences, School of Medicine, Yale University, New Haven, CT, USA
Search for more papers by this authorAydin Arici
Department of Obstetrics, Gynecology & Reproductive Sciences, School of Medicine, Yale University, New Haven, CT, USA
Search for more papers by this authorFrederick Schatz
Department of Obstetrics & Gynecology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA
Search for more papers by this authorCharles J. Lockwood
Department of Obstetrics & Gynecology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA
Search for more papers by this authorCorresponding Author
Umit A. Kayisli
Department of Obstetrics & Gynecology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA
Correspondence
Umit A. Kayisli, Department of Obstetrics & Gynecology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Email: [email protected]
Search for more papers by this authorAbstract
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.
Supporting Information
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| aji12760-sup-0001-FigS1.jpgimage/jpg, 1.7 MB | |
| aji12760-sup-0002-Legends.docxWord document, 12.1 KB |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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