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

After cutaneous injury, a variety of cell types are activated to reconstitute the epithelial and dermal components of the skin. beta-Catenin plays disparate roles in keratinocytes and fibroblasts, inhibiting keratinocyte migration and activating fibroblast proliferation, suggesting that beta-catenin could either inhibit or enhance the healing process. How beta-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 beta-catenin, regulated by an adenovirus expressing cre-recombinase. The size of the wounds in the mice correlated with the protein level of beta-catenin. Using mice expressing these conditional alleles, we found that the wound phenotype imparted by Smad3 deficiency and by the injection of TGFbeta before wounding is mediated in part by beta-catenin. TGFbeta was not able to regulate proliferation in beta-catenin null fibroblasts, whereas keratinocyte proliferation rate was independent of beta-catenin. When mice are treated with lithium, beta-catenin-mediated signaling was activated in cutaneous wounds, which healed with a larger size. These results demonstrate a crucial role for beta-catenin in regulating cutaneous wound size. Furthermore, these data implicate mesenchymal cells as playing a critical role regulating wound size.

Duke Scholars

Author Benjamin Aaron Alman Orthopaedic Surgery