Expression of integrin alphavbeta6 and TGF-beta in scarless vs scar-forming wound healing

Oral mucosal wounds heal with reduced scar formation compared with skin. The epithelial integrin alphavbeta6 is induced during wound healing, and it can activate fibrogenic transforming growth factor beta1 (TGF-beta1) and anti-fibrogenic TGF-beta3 that play key roles in scar formation. In this study, expression of beta6 integrin and members of the TGF-beta pathway were studied in experimental wounds of human gingiva and both gingiva and skin of red Duroc pigs using real-time PCR, gene microarrays, and immunostaining. Similar to human wounds, the expression of beta6 integrin was induced in the pig wounds 7 days after wounding and remained upregulated >49 days. The alphavbeta6 integrin was colocalized with both TGF-beta isoforms in the wound epithelium. Significantly higher expression levels of beta6 integrin and TGF-beta1 were observed in the pig gingival wounds compared with skin. Early gingival wounds also expressed higher levels of TGF-beta3 compared with skin. The spatio-temporal colocalization of alphavbeta6 integrin with TGF-beta1 and TGF-beta3 in the wound epithelium suggests that alphavbeta6 integrin may activate both isoforms during wound healing. Prolonged expression of alphavbeta6 integrin along with TGF-beta3 in the gingival wound epithelium may be important in protection of gingiva from scar formation.