Potential roles of aquaporin 9 in the pathogenesis of endometriosis

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This study found decreased aquaporin 9 expression in endometriosis tissues, and its knockdown in human endometrial stromal cells increased MMPs, activated ERK and p38 MAPK, and enhanced migration and invasion.

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This study evaluated aquaporin (AQP) subtype expression in tissue and explored functional effects of AQP9 in human endometrial stromal cells (HESCs). Women undergoing laparoscopic surgery provided eutopic and ectopic endometrium from endometriosis cases and eutopic endometrium from controls; AQP2 and AQP8 were increased, but only AQP9 showed a significant decrease in eutopic endometrium of endometriosis patients versus controls and differed across groups. In HESCs, transfection with AQP9 siRNA increased MMP2/MMP9 expression, elevated phosphorylated ERK1/2 and p38 MAPK, and enhanced migration and invasion in migration and wound-healing assays. The paper’s findings are limited by its in vitro manipulation in cell culture and the cross-sectional nature of the tissue expression comparisons, and therefore require further investigation. This paper is centrally about endometriosis — specifically, it implicates AQP9 dysregulation and downstream ERK/p38 signaling in endometriosis pathogenesis.

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Abstract

Aquaporins (AQPs) are involved in cell migration, proliferation and carcinogenesis in tumor development and physiologic inflammatory processes, but their associations with endometriosis have not been fully evaluated. In this study, tissue samples were obtained from women undergoing laparoscopic surgery for endometriosis and other benign conditions. Analysis of expressions of AQP subtypes in eutopic and ectopic endometrium of patients with endometriosis (Eu-EMS and Ect-EMS, respectively) and eutopic endometrium of control patients without endometriosis (Eu-CTL) were performed using the NanoString nCounter System and western blotting. Human endometrial stromal cells (HESCs) were cultured and transfected with the siRNA of the AQP of interest. Among the AQP1-9 subtypes, endometrial expression of AQP2 and AQP8 was significantly increased, whereas AQP9 expression was significantly decreased in the Eu-EMS group compared to the Eu-CTL group. Comparison of expression of AQP2, AQP8 and AQP9 among Eu-EMS, Ect-EMS and Eu-CTL groups revealed significant differences for only AQP9. Expression of AQP9 in the Eu-EMS group was decreased compared with that in Eu-CTL. After transfection of AQP9 siRNA in HESCs, expressions of MMP2 and MMP9 were significantly elevated. Increased expression of phosphorylated ERK 1/2 and phosphorylated p38 MAPK proteins after transfection was also confirmed using western blot analysis. Increased migration and invasion potentials of HESCs after transfection were determined by migration and wound healing assays. These findings suggest that AQP9 may be involved in the pathogenesis of endometriosis and warrant further investigation as a potential therapeutic target for treating endometriosis.
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YUHASpace Repository 0 796 Cited 0 times in Cited 13 times in Potential roles of aquaporin 9 in the pathogenesis of endometriosis - Authors - Young Sik Choi ; Ji Hyun Park ; Jeong-Kee Yoon ; Ji Sun Yoon ; Jung Sook Kim ; Jae Hoon Lee ; Bo Hyun Yun ; Joo Hyun Park ; Seok Kyo Seo ; SiHyun Cho ; Byung Seok Lee ; Hugh S.Taylor - Citation - Molecular Human Reproduction, Vol.25(7) : 373-384, 2019 - Journal Title - MOLECULAR HUMAN REPRODUCTION - ISSN - 1360-9947 - Issue Date - 2019 - Keywords - AQP9 ; aquaporins ; endometriosis ; extracellular signal-regulated kinase 1/2 ; matrix metalloproteinase ; migration ; p38 mitogen-activated protein kinases ; pathogenesis ; siRNA ; transfection - Abstract - Aquaporins (AQPs) are involved in cell migration, proliferation and carcinogenesis in tumor development and physiologic inflammatory processes, but their associations with endometriosis have not been fully evaluated. In this study, tissue samples were obtained from women undergoing laparoscopic surgery for endometriosis and other benign conditions. Analysis of expressions of AQP subtypes in eutopic and ectopic endometrium of patients with endometriosis (Eu-EMS and Ect-EMS, respectively) and eutopic endometrium of control patients without endometriosis (Eu-CTL) were performed using the NanoString nCounter System and western blotting. Human endometrial stromal cells (HESCs) were cultured and transfected with the siRNA of the AQP of interest. Among the AQP1-9 subtypes, endometrial expression of AQP2 and AQP8 was significantly increased, whereas AQP9 expression was significantly decreased in the Eu-EMS group compared to the Eu-CTL group. Comparison of expression of AQP2, AQP8 and AQP9 among Eu-EMS, Ect-EMS and Eu-CTL groups revealed significant differences for only AQP9. Expression of AQP9 in the Eu-EMS group was decreased compared with that in Eu-CTL. After transfection of AQP9 siRNA in HESCs, expressions of MMP2 and MMP9 were significantly elevated. Increased expression of phosphorylated ERK 1/2 and phosphorylated p38 MAPK proteins after transfection was also confirmed using western blot analysis. Increased migration and invasion potentials of HESCs after transfection were determined by migration and wound healing assays. These findings suggest that AQP9 may be involved in the pathogenesis of endometriosis and warrant further investigation as a potential therapeutic target for treating endometriosis. - Appears in Collections: - 1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers - Yonsei Authors - Kim, Jeong Sook(김정숙) Park, Joo Hyun(박주현) Seo, Seok Kyo(서석교) https://orcid.org/0000-0003-3404-0484 Yun, Bo Hyon(윤보현) https://orcid.org/0000-0001-5703-797X Yun, Jisun(윤지선) Lee, Byung Seok(이병석) https://orcid.org/0000-0001-6001-2079 Lee, Jae Hoon(이재훈) https://orcid.org/0000-0003-4223-1395 Cho, Si Hyun(조시현) https://orcid.org/0000-0003-2718-6645 Choi, Young Sik(최영식) https://orcid.org/0000-0002-1157-4822 Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

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Condition tags

endometriosis

MeSH descriptors

Aquaporins Endometriosis Endometriosis Adult Aquaporin 2 Aquaporin 2 Aquaporins Cell Movement Cell Movement Cell Movement Endometriosis Endometrium Endometrium Endometrium Female Humans In Vitro Techniques Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3

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