Vitamin D and calcium regulation of epidermal wound healing

J Steroid Biochem Mol Biol. 2016 Nov;164:379-385. doi: 10.1016/j.jsbmb.2015.08.011. Epub 2015 Aug 14.


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.

Keywords: Calcium; Epidermis; Keratinocytes; Stem cells; Vitamin D receptor; Wound repair.

Publication types

  • Review

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Signaling
  • Cell Movement
  • Cell Proliferation
  • Epidermal Cells
  • Epidermis / injuries
  • Epidermis / metabolism*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Keratinocytes / cytology
  • Keratinocytes / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, Calcitriol / deficiency
  • Receptors, Calcitriol / genetics*
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Transcription, Genetic
  • Vitamin D / metabolism*
  • Wound Healing / genetics*
  • Wounds, Penetrating / genetics
  • Wounds, Penetrating / metabolism*
  • Wounds, Penetrating / pathology
  • beta Catenin / genetics*
  • beta Catenin / metabolism


  • CTNNB1 protein, mouse
  • Receptors, Calcitriol
  • beta Catenin
  • Vitamin D
  • Calcium