title: Estradiol-mediated hepatocyte growth factor is involved in the implantation of endometriotic cells via the mesothelial-to-mesenchymal transition in the peritoneum.
abstract: The pathogenesis of endometriosis, a chronic painful gynecological disease characterized by the presence of endometrial tissue located outside of the uterus and often adhering to the peritoneum, is known to be estrogen dependent. However, the precise pathophysiology of endometriosis remains elusive. Recent studies indicate that the epithelial-to-mesenchymal transition (EMT) of human endometrial cells is important for the progression of endometriosis, and another previous study has implicated hepatocyte growth factor (HGF) in endometriosis progression. The aim of the present study was to examine the role of estradiol in the regulation of HGF production and progression of peritoneal endometriosis, focusing on the interactions between the peritoneum and endometriotic cells. Consequently, estradiol was found to promote the proliferation, invasion, and migration of immortalized human endometrial epithelial cells (hEECs) via HGF upregulation, and the estradiol-induced direct binding of estrogen receptor-α to the HGF promoter was confirmed on a chromatin immunoprecipitation (ChIP) assay. Estradiol also induced the EMT in hEECs by promoting HGF production. Furthermore, human mesothelial cells underwent the mesothelial-to-mesenchymal transition (MMT) during culture with estradiol-stimulated hEEC conditioned medium. Importantly, estradiol itself did not induce the MMT, and the estradiol-stimulated hEEC-conditioned medium in the presence of HGF antibodies reversed the MMT process. These results, which were obtained using immortalized hEECs, indicate that estradiol-induced HGF production may play a crucial role in the peritoneal implantation of human endometriotic cells by exerting proliferative and invasive effects via the EMT in hEECs and promoting the MMT in mesothelial cells.
authors: Department of Obstetrics and Gynecology, Osaka Medical College, Osaka, Japan.
authors: Yoshihiro J
authors: YJ
authors: Ono
authors: Department of Obstetrics and Gynecology, Osaka Medical College, Osaka, Japan gyn122@poh.osaka-med.ac.jp.
authors: Masami
authors: M
authors: Hayashi
authors: Department of Obstetrics and Gynecology, Osaka Medical College, Osaka, Japan.
authors: Akiko
authors: A
authors: Tanabe
authors: Department of Obstetrics and Gynecology, Osaka Medical College, Osaka, Japan.
authors: Atsushi
authors: A
authors: Hayashi
authors: Department of Obstetrics and Gynecology, Osaka Medical College, Osaka, Japan.
authors: Masanori
authors: M
authors: Kanemura
authors: Department of Obstetrics and Gynecology, Osaka Medical College, Osaka, Japan.
authors: Yoshito
authors: Y
authors: Terai
authors: Department of Obstetrics and Gynecology, Osaka Medical College, Osaka, Japan.
authors: Masahide
authors: M
authors: Ohmichi
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D004715:Endometriosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D010532:Peritoneal Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010537:Peritoneum / Q000187:drug effects / Q000473:pathology*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D004958:Estradiol; D017228:Hepatocyte Growth Factor
keywords: endometriosis; epithelial-to-mesenchymal transition; estradiol; hepatocyte growth factor; mesothelial-to-mesenchymal transition