Abstract
Cell membrane ion channels have important roles in cell migration during cancer development and metastasis. Although endometriosis is a benign gynecological disease, some migration and invasion characteristics of endometriosis are similar to those of cancer. However, only a few studies have examined cell membrane ion channels and their associations with endometriosis. This study aimed to investigate the effects of these ion channels on development of endometriosis. A total of 39 women who underwent laparoscopic ovarian cyst enucleation were included in the study population. Eutopic endometrium or ectopic endometrium tissues were obtained from each patient based on allocation to an endometriosis group (n=21) or a control group (n=18). Quantitative real-time PCR (qRT-PCR) and western blot analyses were performed to quantify NKCC1, NKCC2, and CLCN3 mRNA expression and protein concentrations. SiRNA transfection and migration assays of the endometrial stromal cells were performed to test the effects of the ion channels on the migration ability. The qRT-PCR and western blot analyses revealed significantly elevated mRNA expression and protein expression of NKCC1, NKCC2, and CLCN3 in the ectopic endometrial tissue from the patients with endometriosis (p < 0.05). Migration assay of siRNA transfected cells suggested a decreased migratory potential of the endometrial stromal cells (p < 0.001). The magnitudes of expression of NKCC1, NKCC2, and CLCN3 were positively correlated with endometrioma size. The increased expression of NKCC1, NKCC2, and CLCN3 in endometriosis offers opportunities to understand mechanisms of endometriosis and develop novel therapeutic approaches.
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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Change history
18 March 2021
The article was updated to include an Article Note that Inha Lee and Dr. Myung Jae Jeon equally contributed to this work.
24 March 2021
A Correction to this paper has been published: https://doi.org/10.1007/s43032-021-00551-0
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Funding
This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI18C2047).
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All authors were responsible for acquisition of data, analysis and interpretation of data, and final approval of the version to be published. Inha Lee, Myung Jae Jeon, Jeong Sook Kim, Ji Hyun Park, SiHyun Cho, and Byung Seok Lee have made substantial contributions for conception and design. Inha Lee and Myung Jae Jeon have equally contributed in drafting the manuscript and SiHyun Cho revised the manuscript critically for important intellectual content.
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The study was performed after approval from the Institutional Review Board of Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea (IRB approval no. 3-2018-0231).
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Each patient provided informed written consent and the hospital’s ethics committees approved enrollment in the study.
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Inha Lee and Dr. Myung Jae Jeon equally contributed to this work.
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Lee, I., Jeon, M.J., Kim, J.S. et al. Aberrant Expression of Sodium-Potassium-Chloride Cotransporter in Endometriosis. Reprod. Sci. 28, 2641–2648 (2021). https://doi.org/10.1007/s43032-021-00531-4
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DOI: https://doi.org/10.1007/s43032-021-00531-4