Beta‐catenin regulates wound size and mediates the effect of TGF‐beta in cutaneous healing

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Abstract
After cutaneous injury, a variety of cell types are activated to reconstitute the epithelial and dermal components of the skin. β-Catenin plays disparate roles in keratinocytes and fibroblasts, inhibiting keratinocyte migration and activating fibroblast proliferation, suggesting that β-catenin could either inhibit or enhance the healing process. How β-catenin functions in concert with other signaling pathways important in the healing process is unknown. Wound size was examined in mice expressing conditional null or conditional stabilized alleles of β-catenin, regulated by an adenovirus expressing cre-recombinase. The size of the wounds in the mice correlated with the protein level of β-catenin. Using mice expressing these conditional alleles, we found that the wound phenotype imparted by Smad3 deficiency and by the injection of TGFβ before wounding is mediated in part by β-catenin. TGFβ was not able to regulate proliferation in β-catenin null fibroblasts, whereas keratinocyte proliferation rate was independent of β-catenin. When mice are treated with lithium, β-catenin-mediated signaling was activated in cutaneous wounds, which healed with a larger size. These results demonstrate a crucial role for β-catenin in regulating cutaneous wound size. Furthermore, these data implicate mesenchymal cells as playing a critical role regulating wound size.—Cheon, S. S., Wei, Q., Gurung, A., Youn, A., Bright, T., Poon, R., Whetstone, H., Guha, A., Alman, B. A. Beta-catenin regulates wound size and mediates the effect of TGF-beta in cutaneous healing.
Funding Information
  • Canadian Institutes of Health Research
  • Canada Excellence Research Chairs, Government of Canada