title: Aquaporin 5 Plays a Role in Estrogen-Induced Ectopic Implantation of Endometrial Stromal Cells in Endometriosis.
abstract: 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.
authors.affiliation: Department of Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou City, Zhejiang Province, China, 310006.
authors.forename: Xiu Xiu
authors.initials: XX
authors.lastname: Jiang
authors.affiliation: Department of Laboratory, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou City, Zhejiang Province, China, 310006.
authors.forename: Xiang Wei
authors.initials: XW
authors.lastname: Fei
authors.affiliation: Department of Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou City, Zhejiang Province, China, 310006.
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Laboratory, School of Medicine, Ningbo University, Ningbo City, Zhejiang Province, China, 315000.
authors.forename: Xiao Lei
authors.initials: XL
authors.lastname: Ye
authors.affiliation: Department of Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou City, Zhejiang Province, China, 310006.
authors.forename: Liao Bin
authors.initials: LB
authors.lastname: Xin
authors.affiliation: Department of Laboratory, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou City, Zhejiang Province, China, 310006.
authors.forename: Yang
authors.initials: Y
authors.lastname: Qu
authors.affiliation: Department of Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou City, Zhejiang Province, China, 310006.
authors.forename: Kai Hong
authors.initials: KH
authors.lastname: Xu
authors.affiliation: Department of Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou City, Zhejiang Province, China, 310006.
authors.forename: Rui Jin
authors.initials: RJ
authors.lastname: Wu
authors.affiliation: Department of Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou City, Zhejiang Province, China, 310006.
authors.forename: Jun
authors.initials: J
authors.lastname: Lin
mesh_terms: D000328:Adult; D000818:Animals; D051402:Aquaporin 5 / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D004715:Endometriosis / Q000378:metabolism / Q000628:therapy*; D004717:Endometrium / Q000166:cytology / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020218:Response Elements; D015290:Second Messenger Systems; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism*
chemical_list: C496036:AQP5 protein, human; D051402:Aquaporin 5; D004958:Estradiol; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt