WOUND FLUID-DERIVED HEPARIN-BINDING EGF-LIKE GROWTH-FACTOR (HB-EGF) IS SYNERGISTIC WITH INSULIN-LIKE GROWTH-FACTOR-I FOR BALB MK KERATINOCYTE PROLIFERATION/

Epidermal cell proliferation is required for re-epithelialization duri ng wound repair. Re-epithelialization of partial thickness excisional wounds in pigs is complete by 6 days after injury. The presence of ins ulin-like growth factor-I (IGF-I) and heparin-binding molecules that a re mitogenic for keratinocytes was examined in wound fluid obtained da ily from these wounds, Two significant heparin-binding growth factor a ctivities for Balb/MK keratinocytes were detected, a major one that wa s eluted from a heparin affinity column with 1.1 M NaCl and a minor on e with 0.5 M NaCl. These activities appeared 1 day after injury, were maximal by 2-3 days later, and disappeared by 6 days after injury, The molecule eluting with 1.1 M NaCl was heparin-binding EGF-like (HB-EGF ), The levels of IGF-I in wound fluid were 45-90 ng/ml during the firs t 3 days following injury, decreased thereafter, and were not detectab le 6 days after injury. IGF-I at 100 ng/ml, increased HB-EGF mitogenic activity for Balb/MK keratinocytes by 40-50-fold, We conclude that th e synergism between IGF-I and HB-EGF and their relative concentrations at the various days after injury may be important variables for regul ating re-epithelialization during wound repair.