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World J Stem Cells. Jul 26, 2020; 12(7): 604-611
Published online Jul 26, 2020. doi: 10.4252/wjsc.v12.i7.604
Vitamin D and calcium signaling in epidermal stem cells and their regeneration
Yuko Oda, Daniel D Bikle
Yuko Oda, Daniel D Bikle, Department of Medicine, University of California San Francisco, CA 94158, United States
Yuko Oda, Daniel D Bikle, Endocrine Research, Veterans Affairs Medical Center San Francisco, CA 94158, United States
Author contributions: Oda Y overviewed related studies, prepared a model and wrote the review paper; Bikle DD reviewed and edited the paper.
Supported by the National Institute of Health (NIH) grant, No. R21 DE025357 (to Oda Y), and No. R01 AR050023 (to Bikle DD); DOD grant, No. CA110338 (to Bikle DD); and VA Merit, No. I01 BX003814-01 (to Bikle DD).
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Yuko Oda, PhD, Associate Research Scientist, Endocrine Research 111N-MB 630, Veterans Affairs Medical Center San Francisco, University of California San Francisco, 1700 Owens Street, San Francisco, CA 94158, United States. yuko.oda@ucsf.edu
Received: February 25, 2020
Peer-review started: February 25, 2020
First decision: April 22, 2020
Revised: May 18, 2020
Accepted: June 10, 2020
Article in press: June 10, 2020
Published online: July 26, 2020
Abstract

Epidermal stem cells (SCs) residing in the skin play an essential role for epidermal regeneration during cutaneous wound healing. Upon injury, distinct epidermal SCs residing in the interfollicular epidermis and/or hair follicles are activated to proliferate. Subsequently, SCs and progeny migrate, differentiate and restore the epidermis. We review a role of the vitamin D signaling through its receptor of vitamin D receptor (Vdr) in these processes. Vdr conditional knockout (cKO) mouse skin experiences a delay in wound re-epithelialization under low dietary calcium conditions, stimulating our efforts to examine a cooperative role of Vdr with calcium signaling through the calcium sensing receptor in the epidermis. We review the role of vitamin D and calcium signaling in different processes essential for injury induced epidermal regeneration during cutaneous wound repair. First, we discuss their roles in self-renewal of epidermal SCs through β-catenin signaling. Then, we describe epidermal remodeling, in which SCs and progeny migrate and differentiate to restore the epidermis, events controlled by the E-cadherin mediated adherens junction signaling. Finally, we discuss the potential mechanisms for vitamin D and calcium signaling to regulate injury induced epidermal regeneration mutually and interdependently.

Keywords: Vitamin D, Calcium, Stem cells, Epidermis, Regeneration, Wound healing

Core tip: Vitamin D and calcium signaling play critical roles in epidermal stem cells and progeny to regenerate the epidermis during cutaneous wound healing. Their regulation of these processes is mediated at least in part through β-catenin and E-cadherin mediated adherens junction signaling.