The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/2/297/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 3, February 2, 1998 297-306

Articles

Role of Nerve Growth Factor in Cutaneous Wound Healing: Accelerating Effects in Normal and Healing-impaired Diabetic Mice

Hiroshi Matsuda*, Hiromi Koyama*, Hiroaki Sato*, Junko Sawada*, Atsuko Itakura*, Akane Tanaka*, Masahiro Matsumoto*, Katsuhiko Konno{ddagger}, Hiroko Ushio*, and Kuniko Matsuda*

From the * Department of Veterinary Clinic, and the {ddagger} Department of Veterinary Internal Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo 183, Japan

Four full-thickness skin wounds made in normal mice led to the significant increase in levels of nerve growth factor (NGF) in sera and in wounded skin tissues. Since sialoadenectomy before the wounds inhibited the rise in serum levels of NGF, the NGF may be released from the salivary gland into the blood stream after the wounds. In contrast, the fact that messenger RNA and protein of NGF were detected in newly formed epithelial cells at the edge of the wound and fibroblasts consistent with 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 mice 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 tissue, and the density of extracellular matrix were observed. NGF also increased the breaking strength of healing linear wounds in normal and diabetic mice. These findings suggested that NGF immediately and constitutively released in response to cutaneous injury may contribute to wound healing through broader biological activities, and NGF improved the diabetic impaired response of wound healing.

Address correspondence to Hiroshi Matsuda, Department of Veterinary Clinic, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183, Japan. Phone: 81-423-67-5784; Fax: 81-423-60-8830; E-mail: hiro{at}cc.tuat.ac.jp

1 Abbreviations used in this paper: bFGF, basic FGF; EGF, epidermal growth factor; FGF, fibroblast growth factor; mRNA, messenger RNA; NGF, nerve growth factor; PDGF, platelet-derived growth factor.


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