Human plasma fibronectin potentiates the mitogenic activity of platelet-derived growth factor and complements its wound healing effects.
Integrin-mediated cell adhesion and growth factor stimuli are both required for optimal control of cell proliferation. In the context of skin injury, cell-derived fibronectin and platelet-derived growth factor play important roles in the stimulation of cell proliferation and migration, activities that are crucial to the healing process. To assess the ability of exogenously supplied plasma-derived fibronectin to stimulate wound repair and to study its ability to cooperate with platelet-derived growth factor-BB during healing, we devised a novel topical delivery formulation that allows the controlled release of both molecules to a wound. Using this topical formulation and the rabbit ear model of dermal wound healing, we show that plasma fibronectin is a potent stimulator of the wound healing process. We also show that administration of fibronectin and platelet-derived growth factor-BB in combination has additive wound healing effects. Finally, we report novel findings on the ability of soluble plasma fibronectin to potentiate the mitogenic effects of platelet-derived growth factor-BB in vitro. These findings not only show that optimal concentrations of exogenous fibronectin administered using an effective delivery system stimulate wound healing; they also suggest that PDGF-BB should be administered with fibronectin to achieve optimal therapeutic stimulation of wound healing.
Larivière
Benoît
B
Dermacor Inc., Sainte-Foy, Québec, Canada.
Rouleau
Michèle
M
Picard
Sylvain
S
Beaulieu
André D
AD
D000287:Administration, Topical; D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000077214:Becaplermin; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005353:Fibronectins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005455:Fluorescent Antibody Technique; D006801:Humans; D008934:Mitogens / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D010982:Platelet-Derived Growth Factor / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D020574:Proto-Oncogene Proteins c-sis; D011817:Rabbits; D012867:Skin / Q000187:drug effects / Q000276:immunology* / Q000293:injuries*; D014945:Wound Healing / Q000187:drug effects* / Q000276:immunology*; D014950:Wounds, Penetrating / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology
D043925:Angiogenesis Inducing Agents; D003692:Delayed-Action Preparations; D005353:Fibronectins; D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin