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.
Cheon
Sophia S
SS
Program in Developmental Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Wei
Qingxia
Q
Gurung
Ananta
A
Youn
Andrew
A
Bright
Tamara
T
Poon
Raymond
R
Whetstone
Heather
H
Guha
Abhijit
A
Alman
Benjamin A
BA
D000818:Animals; D049109:Cell Proliferation; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D015603:Keratinocytes / Q000378:metabolism; D008094:Lithium; D045726:Metalloproteases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D045522:Recombinases / Q000378:metabolism; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism* / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology*; D014947:Wounds and Injuries / Q000378:metabolism* / Q000473:pathology*; D051176:beta Catenin / Q000378:metabolism*
D045522:Recombinases; D016212:Transforming Growth Factor beta; D051176:beta Catenin; D008094:Lithium; D045726:Metalloproteases