Platelet-derived growth factor acts via both the Rho-kinase and p38 signaling enzymes to stimulate contraction in an in vitro model of equine wound healing

Horses are more prone to complications in the wound healing process than other species, and problems such as chronic inflammation, delayed epithelialization, poor wound contraction, and exuberant granulation tissue are commonly seen, particularly in wounds on the distal limbs. In comparison, wounds of the oral mucosa heal rapidly in a scarless fashion with a high degree of wound contraction. The effect of platelet-derived growth factor BB (PDGF), insulin-like growth factor (IGF)-1, and transforming growth factor beta 1 (TGE beta 1) on the contraction of a fibroblast-populated collagen matrix (FPCM) as a model of equine wound contraction was investigated using equine oral fibroblasts. The fibroblasts were embedded into floating FPCM and treated with PDGF, IGF-1, and TGF beta 1. The surface areas of the FPCM were determined daily for 5 d. Platelet-derived growth factor significantly stimulated the contraction of the FPCM at an optimal concentration of 10 ng/mL (P = 0.025). Insulin-like growth factor-1 and TGF beta 1 did not significantly affect the contraction of the FPCM relative to the control. To elucidate the mechanisms by which PDGF stimulated contraction of FPCM, the Rho-kinase and p38 cell signaling pathways were blocked, resulting in a significant inhibition (P < 0.001) of PDGF-stimulated contraction. Platelet-derived growth factor BB is a potent stimulator of fibroblast migration, and hence the FPCM contraction generated here is probably a result of its effects on cell migration. The results of the present experiment suggest that this effect is stimulated via both the Rho-kinase and p38 signaling pathways in equine oral fibroblasts. (C) 2009 Elsevier Inc. All rights reserved.