Synergistic effect of vitamin D and low concentration of transforming growth factor beta 1, a potential role in dermal wound healing

Burns. 2016 Sep;42(6):1277-86. doi: 10.1016/j.burns.2016.03.009. Epub 2016 May 22.


Dermal wound healing, in which transforming growth factor beta 1 (TGFβ1) plays an important role, is a complex process. Previous studies suggest that vitamin D has a potential regulatory role in TGFβ1 induced activation in bone formation, and there is cross-talk between their signaling pathways, but research on their effects in other types of wound healing is limited. The authors therefore wanted to explore the role of vitamin D and its interaction with low concentration of TGFβ1 in dermal fibroblast-mediated wound healing through an in vitro study. Human dermal fibroblasts were treated with vitamin D, TGFβ1, both, or vehicle, and then the wound healing functions of dermal fibroblasts were measured. To further explore possible mechanisms explaining the synergistic effect of vitamin D and TGFβ1, targeted gene silencing of the vitamin D receptor was performed. Compared to either factor alone, treatment of fibroblasts with both vitamin D and low concentration of TGFβ1 increased gene expression of TGFβ1, connective tissue growth factor, and fibronectin 1, and enhanced fibroblast migration, myofibroblast formation, and collagen production. Vitamin D receptor gene silencing blocked this synergistic effect of vitamin D and TGFβ1 on both collagen production and myofibroblast differentiation. Thus a synergistic effect of vitamin D and low TGFβ1 concentration was found in dermal fibroblast-mediated wound healing in vitro. This study suggests that supplementation of vitamin D may be an important step to improve wound healing and regeneration in patients with a vitamin D deficiency.

Keywords: Cross talk of vitamin D and transforming growth factor beta; Wound healing.

MeSH terms

  • Adult
  • Calcitriol / pharmacology*
  • Cell Differentiation / drug effects
  • Cell Movement / drug effects
  • Cells, Cultured
  • Chromatography, Liquid
  • Connective Tissue Growth Factor / drug effects
  • Connective Tissue Growth Factor / genetics
  • Dermis / drug effects*
  • Dermis / metabolism
  • Drug Synergism
  • Female
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Fibronectins / drug effects
  • Fibronectins / genetics
  • Humans
  • Hydroxyproline / metabolism
  • In Vitro Techniques
  • Mass Spectrometry
  • Myofibroblasts / drug effects
  • Real-Time Polymerase Chain Reaction
  • Receptors, Calcitriol / drug effects
  • Receptors, Calcitriol / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Smad2 Protein / drug effects
  • Smad2 Protein / genetics
  • Smad3 Protein / drug effects
  • Smad3 Protein / genetics
  • Smad7 Protein / drug effects
  • Smad7 Protein / genetics
  • Transforming Growth Factor beta1 / drug effects
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / pharmacology*
  • Vitamins / pharmacology*
  • Wound Healing / drug effects*


  • FN1 protein, human
  • Fibronectins
  • Receptors, Calcitriol
  • SMAD2 protein, human
  • SMAD3 protein, human
  • SMAD7 protein, human
  • Smad2 Protein
  • Smad3 Protein
  • Smad7 Protein
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • VDR protein, human
  • Vitamins
  • Connective Tissue Growth Factor
  • Calcitriol
  • Hydroxyproline