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* Program in Developmental Biology, The Hospital for Sick Children, Toronto, Ontario, Canada;
The Institute for Medical Science, University of Toronto, Toronto, Ontario Canada;
Program in Cancer Research, Arthur and Sonia Labatts Brain Tumor Center, The Hospital for Sick Children, Toronto, Ontario, Canada; and
The Department of Surgery, University of Toronto, Toronto, Ontario, Canada
1Correspondence: 555 University Ave., Toronto, Ontario M5G1X8, Canada. E-mail: benjamin.alman{at}sickkids.ca
After cutaneous injury, a variety of cell types are activated to reconstitute the epithelial and dermal components of the skin. ß-Catenin plays disparate roles in keratinocytes and fibroblasts, inhibiting keratinocyte migration and activating fibroblast proliferation, suggesting that ß-catenin could either inhibit or enhance the healing process. How ß-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 ß-catenin, regulated by an adenovirus expressing cre-recombinase. The size of the wounds in the mice correlated with the protein level of ß-catenin. Using mice expressing these conditional alleles, we found that the wound phenotype imparted by Smad3 deficiency and by the injection of TGFß before wounding is mediated in part by ß-catenin. TGFß was not able to regulate proliferation in ß-catenin null fibroblasts, whereas keratinocyte proliferation rate was independent of ß-catenin. When mice are treated with lithium, ß-catenin-mediated signaling was activated in cutaneous wounds, which healed with a larger size. These results demonstrate a crucial role for ß-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.
Key Words: ß-catenin • wound healing • transgenic mice
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