Vitamin D and calcium signaling in epidermal stem cells and their regeneration

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.

Regulation of zebrafish fin regeneration by vitamin D signaling

“…Whereas this study has focused on the description of endogenous vitamin D pathway activity during appendage regeneration and the effects of modulating pathway activity, there remains much to explore on the mechanistic side. The pro‐regenerative effect of vitamin D on fin regeneration is at least in part a local rather than systemic effect, and possible mechanisms by which vitamin D may act are regulation of calcium signaling, 34 energy metabolism and control of oxidative stress, 35,36 or stimulation of FGF ligand secretion by secreted factors from chondrocytes 37 . Although most research studies on vitamin D have assessed mammals, these mechanisms could individually or together contribute to mitogenic effects during fin regeneration in teleosts.…”

Ligand‐Independent Actions of the Vitamin D Receptor: More Questions Than Answers

“…An example of this is the effect of calcium on the translocation of E‐cadherin to the membrane after calcium administration, which is blunted in keratinocytes lacking the VDR. ( 82 ) Thus, calcium stimulation of keratinocyte differentiation does not appear to depend on 1,25(OH) 2 D, but at least some of its actions require VDR in the absence of 1,25(OH) 2 D.…”

Nanomaterials in Skin Regeneration and Rejuvenation

“…Then, the proliferative phase occurs, when regeneration restores skin functions. The main actors of these events are stem cells and fibroblasts, that, by migrating to the damaged site, take care of extracellular matrix depot and inflammatory mediators secretion [26,27]. Fibroblasts are responsible for wound closure, from the early inflammatory phase to the final phase comprising extracellular matrix production, essential to restore skin barrier [26].…”

“…Fibroblasts are responsible for wound closure, from the early inflammatory phase to the final phase comprising extracellular matrix production, essential to restore skin barrier [26]. Additionally, stem cells are involved in skin regeneration, undergoing proliferation and differentiation toward keratinocytes and/or fibroblasts before the final re-epithelization [13,27].…”

“…Bioactive molecules, properly delivered, can implement regenerative and rejuvenating processes supported by skin cell populations. Moreover, a suitable formulation can modulate molecule release, increasing drug solubility [20,27,[33][34][35][36]. Nanomedicine discloses novel chances for innovative pharmacotherapeutic approaches enhancing the passive penetration and increasing the thermodynamic activity of drugs [37,38].…”