Figure 9.

A simplified illustration depicting how pericytes differentiate to matrix-producing myofibroblasts. Chemotactic PDGF, TGF-β1, and CCN2/CTGF signaling by platelets and macrophages causes the pericytes to detach from the vessel wall and produce EDA FN and collagen. Full differentiation of pericytes into myofibroblasts, evidenced by αSMA expression, depends on three essential elements, namely TGF-β1, EDA FN, and tension that can be created in the matrix produced by the pericytes. Myofibroblasts interact with EDA FN via α₅β₁, α_vβ₃, and α_vβ₅ integrins and with collagen via α₂β₁ and α₁₁β₁ integrins. Latent TGF-β1 complex is bound into the FN matrix and possibly activated via α_vβ₅ integrin and by other mechanisms. Whether the wound heals scarless, with scars, or becomes fibrotic depends on both the presence of myofibroblasts and macrophage-derived TGF-β1. αSMA, alpha–smooth muscle actin; CCN, Cyr61-CTGF-Nov; CTGF, connective tissue growth factor. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/wound