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Role of Epithelial-Mesenchymal Transition in Human Adenomyosis: A New Insight into Its Pathogenesis

Chapter
Part of the Comprehensive Gynecology and Obstetrics book series (CGO)

Abstract

The exact pathogenesis of adenomyosis is still elusive. Among different reported concepts, direct invagination of gland cells from basalis endometrium deep into myometrium is the most widely accepted opinion in the development of adenomyosis. To address the mechanistic basis of this accepted concept, we investigated the role of hepatocyte growth factor (HGF) and estrogen in the occurrence of epithelial-mesenchymal transition (EMT) in human adenomyosis. Biopsy specimens from endometrium to myometrium were collected after hysterectomy from women with and without adenomyosis. The relationship between HGF and E-cadherin (epithelial cell marker)/N-cadherin (mesenchymal cell marker) was examined using endometrial epithelial cells (EECs) and tissues by qRT-PCR and immunohistochemistry. The gene and protein expressions of two transcriptional repressors of E-cadherin, SLUG and SNAIL, were examined using Ishikawa cells. HGF downregulated E-cadherin and upregulated N-cadherin mRNA expression in EECs, and an inverse relationship between HGF and E-cadherin was observed in basalis endometria of women with adenomyosis. HGF induced morphological changes and promoted migration of EECs. Ishikawa cells exhibited upregulation of SLUG/SNAIL gene expression in response to HGF and estrogen with an additive effect between them. HGF- and estrogen-promoted SLUG/SNAIL gene expression was significantly abrogated after pretreatment of cells with anti-HGF antibody or ICI 182720, an estrogen receptor antagonist. Our findings suggested that HGF either alone or in combination with estrogen may be involved in gland invagination deep into myometrium by inducing EMT in women with adenomyosis.

Keywords

Adenomyosis Basalis endometrium HGF EMT Pathogenesis 

Notes

Acknowledgment

This work was supported in part by Grants-in-Aid for Scientific Research (grants 21592101 and 24592474) from the Japan Society of the Promotion of Science (to K.N.K.).

I gratefully thank Dr. Akira Fujishita and Dr. Koichi Hiraki of Saikeikai Nagasaki Hospital and Dr. Michio Kitajima of Nagasaki University Hospital for their kind assistance in sample collection and Prof. Masahiro Nakashima for his experimental advice. K.N.K. designed and supervised the project and edited/wrote the complete draft.

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Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Department of Obstetrics and Gynecology, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan

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