Vitamin D Proliferates Vaginal Epithelium through RhoA Expression in Postmenopausal Atrophic Vagina tissue
Arum Lee1,5, Man Ryul Lee3,5, Hae-Hyeog Lee2, Yeon-Suk Kim1, Jun-Mo Kim4, Temuulee Enkhbold1,
and Tae-Hee Kim2,*
1Department of Interdisciplinary Program in Biomedical Science, Soonchunhyang University Graduate School, Asan 31538, Korea,
2Department of Obstetrics and Gynecology, Soonchunhyang University College of Medicine, Bucheon 14584, Korea,
3Soonchunhyang Institute of Medi-bio Science (SIMS) and Institute of Tissue Regeneration, College of Medicine, Soon Chun
Hyang University, Cheonan 31151, Korea, 4Departments of Urology, Soonchunhyang University College of Medicine, Bucheon
14584, Korea, 5These authors contributed equally to this work.
Received February 19, 2017; Revised June 25, 2017; Accepted July 14, 2017.; Published online August 25, 2017.
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Postmenopausal atrophic vagina (PAV) is the thinning of the walls of the vagina and decreased lugae of the vagina. PAV is caused by decreased estrogen levels in postmenopausal women. However, the harmful effects of hormone replacement therapy (HRT) have resulted in considerable caution in its use. Various estrogen agonist treatment options are available. Vitamin D is influences the regulation of differentiation and proliferation of various cells, especially tissues lining stratified squamous epithelium, such as the vaginal epithelium. In this study, we hypothesized that vitamin D could provide an alternative and a safe treatment option for PAV by promoting the proliferation and differentiation of the vaginal epithelium. Thirty six patients were enrolled in this case-control study. Vitamin D associated proteins in a vitamin D and sex hormone treated vaginal epithelial cell line as well as normal and PAV tissues were measured. To confirm of cell-to-cell junction protein expression, cell line and tissue studies included RTPCR, immunohistochemistry staining, and immunoblot analyses. The expression of cell-to-cell junction proteins was higher in women with symptoms of atrophic vagina tissue compared to women without the symptoms. Vitamin D stimulated the proliferation of the vaginal epithelium by activating p- RhoA and Erzin through the vitamin D receptor (VDR). The results suggest that vitamin D positively regulates cell-to-cell junction by increasing the VDR/p-RhoA/p-Ezrin pathway. This is the first study to verify the relationship of the expression of RhoA and Ezrin proteins in vaginal tissue of PAV.
Keywords: cholecalciferol, ezrin, rho A, vagina

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