ROLE OF NERVE GROWTH-FACTOR IN CUTANEOUS WOUND-HEALING - ACCELERATINGEFFECTS IN NORMAL AND HEALING-IMPAIRED DIABETIC MICE

Four full-thickness skin wounds made in normal mice led to the signifi cant increase in levels of nerve growth factor (NGF) in sera and in wo unded skin tissues. Since sialoadenectomy before the wounds inhibited the nse in serum levels of NGF, the NGF may be released from the saliv ary gland into the blood stream after the wounds. In contrast, the fac t that messenger RNA and protein of NGF were detected in newly formed epithelial cells at the edge of the wound and fibroblasts consistent w ith the granulation tissue produced in the wound space, suggests that NGF was also produced at the wounded skin site. Topical application of NGF into the wounds accelerated the rate of wound healing in normal m ice and in healing-impaired diabetic KK/Ta mice. This clinical effect of NGF was evaluated by histological examination; the increases in the degree of reepithelialization, the thickness of the granulation tissu e, and the density of extracellular matrix were observed. NGF also inc reased the breaking strength of healing linear wounds in normal and di abetic mice. These findings suggested that NGF immediately and constit utively released in response to cutaneous injury may contribute to wou nd healing through broader biological activities, and NGF improved the diabetic impaired response of wound healing.