ReviewVitamin D and calcium regulation of epidermal wound healing

- Deleting the vitamin D receptor (VDR) from keratinocytes (epiVDRKO) in combination with a low calcium diet delays skin wound healing.
- The delay in wound healing is accompanied by a reduction in β-catenin signaling.
- Proliferation and migration of the keratinocytes at the edge of the wound are reduced in the epiVDRKO as is the expression of axin 2, indicating the role of β-catenin signaling in the epidermal response to wounding and its dependence on the VDR.

Wound healing is essential for survival. This is a multistep process involving a number of different cell types. In the skin wounding triggers an acute inflammatory response, with the innate immune system contributing both to protection against invasive organisms and to triggering the invasion of inflammatory cells into the wounded area. These cells release a variety of cytokines and growth factors that stimulate the proliferation and migration of dermal and epidermal cells to close the wound. In particular, wounding activates stem cells in the interfollicular epidermis (IFE) and hair follicles (HF) to proliferate and send their progeny to re-epithelialize the wound. β-catenin and calcium signaling are important for this activation process. Mice lacking the VDR when placed on a low calcium diet have delayed wound healing. This is associated with reduced β-catenin transcriptional activity and proliferation in the cells at the leading edge of wound closure. These data suggest that vitamin D and calcium signaling are necessary components of the epidermal response to wounding, likely by regulating stem cell activation through increased β-catenin transcriptional activity.