Figure 6.

A schematic presentation of KC integrin expression and ECM molecule distribution during human oral mucosal healing. (A) The contact with the ECM molecules and pro-migratory growth factors (e.g., EGF) present in the wound clot activate the wound edge basal KCs. They dissolve their hemidesmosomal contacts with the BM and extend into the wound clot. As they migrate, wound KCs interact with the provisional BM they deposit underneath themselves. In this provisional matrix, they interact with EDA FN via α₅β₁, α₉β₁, and α_vβ₁ integrins, with TN-C via α₉β₁ integrin and with laminin-332 via α₂β₁, α₃β₁, and α₆β₄ integrins. KC migration is sustained by their autocrine expression of HB-EGF. (B) After wound edges have joined, BM is regenerated, and hemidesmosome re-assembly is initiated. At this point, α_vβ₆ integrin expression is induced in the wound KCs. It potentially interacts with and activates latent, ECM-bound TGF-β1 to regulate KC proliferation, inflammation, and granulation tissue remodeling. Migrating wound KCs express α₂β₁, α₃β₁, α₅β₁, α₉β₁, α_vβ₁, and α₆β₄ integrins; suprabasal early-wound KCs express β₁ integrins; late-wound basal KCs express mainly α₂β₁, α₃β₁, α₉β₁, α_vβ₆, and α₆β₄ integrins, whereas the expression of α₅β₁ and α_vβ₁ integrins is downregulated; late wound suprabasal KCs express α_vβ₆ integrin. Mature BM consists mainly of laminin-332, other laminins, collagen types IV and VII, and tenascin-C; provisional BM consists mainly of laminin-332, EDA FN, and tenascin-C. Connective tissue (CT) contains type I collagen, other collagens, and FN. Wound clot (FC) contains fibrin, FN, and vitronectin. Granulation tissue (GT) contains EDA and EDB FNs, collagen types I and III, other collagens, tenascin-C, fibrin, vitronectin. KC, keratinocyte; BM, basement membrane; EDA/B, extra domain A/B; HB-EGF, heparin-binding EGF-like growth factor. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/wound