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Mol Hum Reprod. 2019 May 9. pii: gaz025. doi: 10.1093/molehr/gaz025. [Epub ahead of print]

Potential roles of aquaporin 9 in the pathogenesis of endometriosis.

Choi YS1,2, Park JH3, Yoon JK4, Yoon JS1,2, Kim JS2,3, Lee JH1,2, Yun BH1,2, Park JH2,3, Seo SK1,2, Cho S2,3, Lee BS1,2, Taylor HS5.

Author information

1
Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
2
Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea.
3
Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
4
Department of Medical Engineering, Yonsei University College of Medicine, Seoul, Korea.
5
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA.

Abstract

Aquaporins (AQPs) are involved in cell migration, proliferation, and carcinogenesis in tumor development and physiologic inflammatory processes, but their associations with endometriosis has 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, expression of MMP2 and MMP9 were significantly elevated. Increased expression of phosphorylated ERK 1/2 (p-ERK 1/2) and phosphorylated p38 MAPK (p-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.

KEYWORDS:

AQP9; aquaporins; endometriosis; extracellular signal-regulated kinase 1/2; matrix metalloproteinase; migration; p38 mitogen-activated protein kinases; pathogenesis; siRNA; transfection

PMID:
31070762
DOI:
10.1093/molehr/gaz025

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