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RhoA/ROCK pathway mediates the effect of oestrogen on regulating epithelial‐mesenchymal transition and proliferation in endometriosis

Endometriosis is a benign gynaecological disease appearing with pelvic pain, rising dysmenorrhoea and infertility seriously impacting on 10% of reproductive‐age females. This research attempts to demonstrate the function and molecular mechanism of RhoA/ROCK pathway on epithelial‐mesenchymal transiti...

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Autores principales: Huang, Zhi‐Xiong, Mao, Xiao‐Mei, Wu, Rong‐Feng, Huang, Shao‐Min, Ding, Xin‐Yu, Chen, Qiong‐Hua, Chen, Qing‐Xi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521234/
https://www.ncbi.nlm.nih.gov/pubmed/32725958
http://dx.doi.org/10.1111/jcmm.15689
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author Huang, Zhi‐Xiong
Mao, Xiao‐Mei
Wu, Rong‐Feng
Huang, Shao‐Min
Ding, Xin‐Yu
Chen, Qiong‐Hua
Chen, Qing‐Xi
author_facet Huang, Zhi‐Xiong
Mao, Xiao‐Mei
Wu, Rong‐Feng
Huang, Shao‐Min
Ding, Xin‐Yu
Chen, Qiong‐Hua
Chen, Qing‐Xi
author_sort Huang, Zhi‐Xiong
collection PubMed
description Endometriosis is a benign gynaecological disease appearing with pelvic pain, rising dysmenorrhoea and infertility seriously impacting on 10% of reproductive‐age females. This research attempts to demonstrate the function and molecular mechanism of RhoA/ROCK pathway on epithelial‐mesenchymal transition (EMT) and proliferation in endometriosis. The expression of Rho family was abnormally changed in endometriotic lesions; in particular, RhoA and ROCK1/2 were significantly elevated. Overexpression of RhoA in human eutopic endometrial epithelial cells (eutopic EECs) enhanced the cell mobility, epithelial‐mesenchymal transition (EMT) and proliferation, and RhoA knockdown exhibited the opposite function. Oestrogen up‐regulated the RhoA activity and expression of RhoA and ROCK1/2. RhoA overexpression reinforced the effect of oestrogen on promoting EMT and proliferation, and RhoA knockdown impaired the effect of oestrogen. oestrogen receptor α (ERα) was involved with the regulation of oestrogen on EMT and proliferation and up‐regulated RhoA activity and expression of RhoA and ROCK1/2. The function of ERα was modulated by the change in RhoA expression. Furthermore, phosphorylated ERK that was enhanced by oestrogen and ERα promoted the protein expression of RhoA/ROCK pathway. Endometriosis mouse model revealed that oestrogen enhanced the size and weight of endometriotic lesions. The expression of RhoA and phosphorylated ERK in mouse endometriotic lesions was significantly elevated by oestrogen. We conclude that abnormal activated RhoA/ROCK pathway in endometriosis is responsible for the function of oestrogen/ERα/ERK signalling, which promoted EMT and proliferation and resulted in the development of endometriosis.
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spelling pubmed-75212342020-09-30 RhoA/ROCK pathway mediates the effect of oestrogen on regulating epithelial‐mesenchymal transition and proliferation in endometriosis Huang, Zhi‐Xiong Mao, Xiao‐Mei Wu, Rong‐Feng Huang, Shao‐Min Ding, Xin‐Yu Chen, Qiong‐Hua Chen, Qing‐Xi J Cell Mol Med Original Articles Endometriosis is a benign gynaecological disease appearing with pelvic pain, rising dysmenorrhoea and infertility seriously impacting on 10% of reproductive‐age females. This research attempts to demonstrate the function and molecular mechanism of RhoA/ROCK pathway on epithelial‐mesenchymal transition (EMT) and proliferation in endometriosis. The expression of Rho family was abnormally changed in endometriotic lesions; in particular, RhoA and ROCK1/2 were significantly elevated. Overexpression of RhoA in human eutopic endometrial epithelial cells (eutopic EECs) enhanced the cell mobility, epithelial‐mesenchymal transition (EMT) and proliferation, and RhoA knockdown exhibited the opposite function. Oestrogen up‐regulated the RhoA activity and expression of RhoA and ROCK1/2. RhoA overexpression reinforced the effect of oestrogen on promoting EMT and proliferation, and RhoA knockdown impaired the effect of oestrogen. oestrogen receptor α (ERα) was involved with the regulation of oestrogen on EMT and proliferation and up‐regulated RhoA activity and expression of RhoA and ROCK1/2. The function of ERα was modulated by the change in RhoA expression. Furthermore, phosphorylated ERK that was enhanced by oestrogen and ERα promoted the protein expression of RhoA/ROCK pathway. Endometriosis mouse model revealed that oestrogen enhanced the size and weight of endometriotic lesions. The expression of RhoA and phosphorylated ERK in mouse endometriotic lesions was significantly elevated by oestrogen. We conclude that abnormal activated RhoA/ROCK pathway in endometriosis is responsible for the function of oestrogen/ERα/ERK signalling, which promoted EMT and proliferation and resulted in the development of endometriosis. John Wiley and Sons Inc. 2020-07-29 2020-09 /pmc/articles/PMC7521234/ /pubmed/32725958 http://dx.doi.org/10.1111/jcmm.15689 Text en © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Huang, Zhi‐Xiong
Mao, Xiao‐Mei
Wu, Rong‐Feng
Huang, Shao‐Min
Ding, Xin‐Yu
Chen, Qiong‐Hua
Chen, Qing‐Xi
RhoA/ROCK pathway mediates the effect of oestrogen on regulating epithelial‐mesenchymal transition and proliferation in endometriosis
title RhoA/ROCK pathway mediates the effect of oestrogen on regulating epithelial‐mesenchymal transition and proliferation in endometriosis
title_full RhoA/ROCK pathway mediates the effect of oestrogen on regulating epithelial‐mesenchymal transition and proliferation in endometriosis
title_fullStr RhoA/ROCK pathway mediates the effect of oestrogen on regulating epithelial‐mesenchymal transition and proliferation in endometriosis
title_full_unstemmed RhoA/ROCK pathway mediates the effect of oestrogen on regulating epithelial‐mesenchymal transition and proliferation in endometriosis
title_short RhoA/ROCK pathway mediates the effect of oestrogen on regulating epithelial‐mesenchymal transition and proliferation in endometriosis
title_sort rhoa/rock pathway mediates the effect of oestrogen on regulating epithelial‐mesenchymal transition and proliferation in endometriosis
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521234/
https://www.ncbi.nlm.nih.gov/pubmed/32725958
http://dx.doi.org/10.1111/jcmm.15689
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