Aquaporin 5 Plays a Role in Estrogen-Induced Ectopic Implantation of Endometrial Stromal Cells in Endometriosis.
Aquaporin 5 (AQP5) participates in the migration of endometrial cells. Elucidation of the molecular mechanisms associated with AQP5-mediated, migration of endometrial cells may contribute to a better understanding of endometriosis. Our objectives included identifying the estrogen-response element (E...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2015-01-01
|
Series: | PLoS ONE |
Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0145290&type=printable |
_version_ | 1826584401664802816 |
---|---|
author | Xiu Xiu Jiang Xiang Wei Fei Li Zhao Xiao Lei Ye Liao Bin Xin Yang Qu Kai Hong Xu Rui Jin Wu Jun Lin |
author_facet | Xiu Xiu Jiang Xiang Wei Fei Li Zhao Xiao Lei Ye Liao Bin Xin Yang Qu Kai Hong Xu Rui Jin Wu Jun Lin |
author_sort | Xiu Xiu Jiang |
collection | DOAJ |
description | Aquaporin 5 (AQP5) participates in the migration of endometrial cells. Elucidation of the molecular mechanisms associated with AQP5-mediated, migration of endometrial cells may contribute to a better understanding of endometriosis. Our objectives included identifying the estrogen-response element (ERE) in the promoter region of the AQP5 gene, and, investigating the effects of AQP5 on ectopic implantation of endometrial cells. Luciferase reporter assays and electrophoretic mobility shift assay (EMSA) identified the ERE-like motif in the promoter region of the AQP5 gene. After blocking and up-regulating estradiol (E2) levels, we analysed the expression of AQP5 in endometrial stromal (ES) cells. After blocking E2 /or phosphatidylinositol 3 kinase(PI3K), we analysed the role of AQP5 in signaling pathways. We constructed an AQP5, shRNA, lentiviral vector to knock out the AQP5 gene in ES cells. After knock-out of the AQP5 gene, we studied the role of AQP5 in cell invasion, proliferation, and the formation of ectopic endometrial implants in female mice. We identified an estrogen-response element in the promoter region of the AQP5 gene. Estradiol (E2) increased AQP5 expression in a dose-dependent fashion, that was blocked by ICI182,780(an estrogen receptor inhibitor). E2 activated PI3K /protein kinase B(AKT) pathway (PI3K/AKT), that, in turn, increased AQP5 expression. LY294002(PI3K inhibitor) attenuated estrogen-enhanced, AQP5 expression. Knock-out of the AQP5 gene with AQP5 shRNA lentiviral vector significantly inhibited E2-enhanced invasion, proliferation of ES cells and formation of ectopic implants. Estrogen induces AQP5 expression by activating ERE in the promoter region of the AQP5gene, activates the PI3K/AKT pathway, and, promotes endometrial cell invasion and proliferation. These results provide new insights into some of the mechanisms that may underpin the development of deposits of ectopic endometrium. |
first_indexed | 2024-12-16T08:20:45Z |
format | Article |
id | doaj.art-e89338f2cac646b0b2d2375c37150385 |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2025-03-14T15:37:10Z |
publishDate | 2015-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS ONE |
spelling | doaj.art-e89338f2cac646b0b2d2375c371503852025-02-25T05:32:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011012e014529010.1371/journal.pone.0145290Aquaporin 5 Plays a Role in Estrogen-Induced Ectopic Implantation of Endometrial Stromal Cells in Endometriosis.Xiu Xiu JiangXiang Wei FeiLi ZhaoXiao Lei YeLiao Bin XinYang QuKai Hong XuRui Jin WuJun LinAquaporin 5 (AQP5) participates in the migration of endometrial cells. Elucidation of the molecular mechanisms associated with AQP5-mediated, migration of endometrial cells may contribute to a better understanding of endometriosis. Our objectives included identifying the estrogen-response element (ERE) in the promoter region of the AQP5 gene, and, investigating the effects of AQP5 on ectopic implantation of endometrial cells. Luciferase reporter assays and electrophoretic mobility shift assay (EMSA) identified the ERE-like motif in the promoter region of the AQP5 gene. After blocking and up-regulating estradiol (E2) levels, we analysed the expression of AQP5 in endometrial stromal (ES) cells. After blocking E2 /or phosphatidylinositol 3 kinase(PI3K), we analysed the role of AQP5 in signaling pathways. We constructed an AQP5, shRNA, lentiviral vector to knock out the AQP5 gene in ES cells. After knock-out of the AQP5 gene, we studied the role of AQP5 in cell invasion, proliferation, and the formation of ectopic endometrial implants in female mice. We identified an estrogen-response element in the promoter region of the AQP5 gene. Estradiol (E2) increased AQP5 expression in a dose-dependent fashion, that was blocked by ICI182,780(an estrogen receptor inhibitor). E2 activated PI3K /protein kinase B(AKT) pathway (PI3K/AKT), that, in turn, increased AQP5 expression. LY294002(PI3K inhibitor) attenuated estrogen-enhanced, AQP5 expression. Knock-out of the AQP5 gene with AQP5 shRNA lentiviral vector significantly inhibited E2-enhanced invasion, proliferation of ES cells and formation of ectopic implants. Estrogen induces AQP5 expression by activating ERE in the promoter region of the AQP5gene, activates the PI3K/AKT pathway, and, promotes endometrial cell invasion and proliferation. These results provide new insights into some of the mechanisms that may underpin the development of deposits of ectopic endometrium.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0145290&type=printable |
spellingShingle | Xiu Xiu Jiang Xiang Wei Fei Li Zhao Xiao Lei Ye Liao Bin Xin Yang Qu Kai Hong Xu Rui Jin Wu Jun Lin Aquaporin 5 Plays a Role in Estrogen-Induced Ectopic Implantation of Endometrial Stromal Cells in Endometriosis. PLoS ONE |
title | Aquaporin 5 Plays a Role in Estrogen-Induced Ectopic Implantation of Endometrial Stromal Cells in Endometriosis. |
title_full | Aquaporin 5 Plays a Role in Estrogen-Induced Ectopic Implantation of Endometrial Stromal Cells in Endometriosis. |
title_fullStr | Aquaporin 5 Plays a Role in Estrogen-Induced Ectopic Implantation of Endometrial Stromal Cells in Endometriosis. |
title_full_unstemmed | Aquaporin 5 Plays a Role in Estrogen-Induced Ectopic Implantation of Endometrial Stromal Cells in Endometriosis. |
title_short | Aquaporin 5 Plays a Role in Estrogen-Induced Ectopic Implantation of Endometrial Stromal Cells in Endometriosis. |
title_sort | aquaporin 5 plays a role in estrogen induced ectopic implantation of endometrial stromal cells in endometriosis |
url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0145290&type=printable |
work_keys_str_mv | AT xiuxiujiang aquaporin5playsaroleinestrogeninducedectopicimplantationofendometrialstromalcellsinendometriosis AT xiangweifei aquaporin5playsaroleinestrogeninducedectopicimplantationofendometrialstromalcellsinendometriosis AT lizhao aquaporin5playsaroleinestrogeninducedectopicimplantationofendometrialstromalcellsinendometriosis AT xiaoleiye aquaporin5playsaroleinestrogeninducedectopicimplantationofendometrialstromalcellsinendometriosis AT liaobinxin aquaporin5playsaroleinestrogeninducedectopicimplantationofendometrialstromalcellsinendometriosis AT yangqu aquaporin5playsaroleinestrogeninducedectopicimplantationofendometrialstromalcellsinendometriosis AT kaihongxu aquaporin5playsaroleinestrogeninducedectopicimplantationofendometrialstromalcellsinendometriosis AT ruijinwu aquaporin5playsaroleinestrogeninducedectopicimplantationofendometrialstromalcellsinendometriosis AT junlin aquaporin5playsaroleinestrogeninducedectopicimplantationofendometrialstromalcellsinendometriosis |