Rab25 Deficiency Perturbs Epidermal Differentiation and Skin Barrier Function in Mice
Haengdueng Jeong1,†, Kyung-Min Lim2,†, James R. Goldenring3 and Ki Taek Nam1,*
1Severance Biomedical Science Institute and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722,
2College of Pharmacy, Ewha Womans University, Seoul 03760, Republic of Korea
3Epithelial Biology Center and Department of Surgery, Vanderbilt University School of Medicine and the Nashville VA Medical Center, Nashville, TN 37232, USA
E-mail: kitaek@yuhs.ac
Tel: +82-2-2228-0754, Fax: +82-2-2227-8129
The first two authors contributed equally to this work.
Received: July 22, 2019; Revised: August 6, 2019; Accepted: August 12, 2019; Published online: September 30, 2019.
© The Korean Society of Applied Pharmacology. All rights reserved.

Rab25, a member of the Rab11 small GTPase family, is central to achieving cellular polarity in epithelial tissues. Rab25 is highly expressed in epithelial cells of various tissues including breast, vagina, cervix, the gastrointestinal tract, and skin. Rab25 plays key roles in tumorigenesis, mainly by regulating epithelial differentiation and proliferation. However, its role in skin physiology is relatively unknown. In this study, we demonstrated that Rab25 knock-out (KO) mice show a skin barrier dysfunction with high trans-epidermal water loss and low cutaneous hydration. To examine this observation, we investigated the histology and epidermal differentiation markers of the skin in Rab25 KO mice. Rab25 KO increased cell proliferation at the basal layer of epidermis, whereas the supra-basal layer remained unaffected. Ceramide, which is a critical lipid component for skin barrier function, was not altered by Rab25 KO in its distribution or amount, as determined by immunohistochemistry. Notably, levels of epidermal differentiation markers, including loricrin, involucrin, and keratins (5, 14, 1, and 10) increased prominently in Rab25 KO mice. In line with this, depletion of Rab25 with single hairpin RNA increased the expression of differentiation markers in a human keratinocyte cell line, HaCaT. Transcriptomic analysis of the skin revealed increased expression of genes associated with skin development, epidermal development, and keratinocyte differentiation in Rab25 KO mice. Collectively, these results suggested that Rab25 is involved in the regulation of epidermal differentiation and proliferation.
Keywords: Rab25, Skin, Epidermis, Epidermal differentiation, Skin proliferation

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