Estradiol-mediated hepatocyte growth factor is involved in the implantation of endometriotic cells via the mesothelial-to-mesenchymal transition in the peritoneum

Ono YJ, Yoshihiro Joshua Ono, Yoshihiro J Ono, Hayashi M, Masami Hayashi, Akiko Tanabe, Tanabe A, Atsushi Hayashi, Hayashi A, Masanori Kanemura, Kanemura M, Terai Y, Yoshito Terai, Ohmichi M, Masahide Ohmichi
American journal of physiology. Endocrinology and metabolism · 2015 · vol. 308(11) , pp. E950–E959 · doi:10.1152/ajpendo.00573.2014 · PMID:25852006 · W1982172605
article OA: closed CC0 ⤵ 11 in-corpus citations
View on OpenAlex View on PubMed View at publisher
⚙ AI-generated summary by gemini-2.5-flash-lite, 2026-06-09 ⓘ

Estradiol upregulates hepatocyte growth factor to promote endometriotic cell proliferation, invasion, and migration via epithelial-to-mesenchymal transition, and induces peritoneal mesothelial-to-mesenchymal transition, facilitating endometriosis implantation.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

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.

My notes (saved in your browser only)

Condition tags

endometriosis

MeSH descriptors

Endometriosis Epithelial-Mesenchymal Transition Estradiol Hepatocyte Growth Factor Peritoneal Diseases Peritoneum Adult Case-Control Studies Cell Adhesion Cell Adhesion Cell Adhesion Cell Proliferation Cell Proliferation Cell Proliferation Cells, Cultured Cross-Sectional Studies Endometriosis Endometriosis Endometriosis Epithelial-Mesenchymal Transition

Citation neighborhood (2-hop)

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. Outer rings show 2-hop neighbours — papers reached through the immediate citers/citees. [ collapse to 1-hop ]

References (39)

Cited by (12)

Source provenance

europepmc
last seen: 2026-09-27T09:11:36.575535+00:00
openalex
last seen: 2026-06-10T17:14:06.276822+00:00
pubmed
last seen: 2026-05-13T22:17:58.238279+00:00
License: CC0 · commercial use OK