INDUCTION OF KERATINOCYTE GROWTH-FACTOR EXPRESSION IS REDUCED AND DELAYED DURING WOUND-HEALING IN THE GENETICALLY DIABETIC MOUSE

We have recently demonstrated induction of expression of several membe rs of the fibroblast growth factor family during wound healing, partic ularly for keratinocyte growth factor, which was more than 150-fold in duced within 24 h after injury. To assess whether wound-healing disord ers are associated with a defect in fibroblast growth factor regulatio n, we have now investigated the expression of these mitogens as well a s their receptors in normal and wounded skin of genetically diabetic d b/db mice, which are characterized by their impaired wound healing. We demonstrate that induction of keratinocyte growth factor expression i n these mice is significantly reduced and delayed compared to normal m ice. Induction of acidic fibroblast growth factor (FGP) and basic FGF expression was earlier in diabetic mice than in normal mice, but by 3 d after injury expression of these mitogens had already returned to th e basal levels. In contrast, elevated levels of acidic FGF and basic F GF transcripts were detected within the first 5 d in wounds from norma l mice. Thus, FGFs seem to be expressed in a limited fashion in the wo und tissue of db/db mice during the period when re-epithelialization a nd granulation tissue formation normally occur. These findings provide an explanation for the beneficial effect of exogenous FGF in the trea tment of impaired wound healing in these animals and suggest that indu ction ofKGF early in repair may be critical for the rapid re-epithelia lization in normal wound healing.