Abstract
As a well-known neurotrophic factor, nerve growth factor (NGF) has also been extensively recognized for its acceleration of healing in cutaneous wounds in both animal models and randomized clinical trials. However, the underlying mechanisms accounting for the therapeutic effect of NGF on skin wounds are not fully understood. NGF treatment significantly accelerated the rate of wound healing by promoting wound reepithelialization, the formation of granulation tissue, and collagen production. To explore the possible mechanisms of this process, the expression levels of CD68, VEGF, PCNA, and TGF-β1 in wounds were detected by immunohistochemical staining. The levels of these proteins were all significantly raised in NGF-treated wounds compared to untreated controls. NGF also significantly promoted the migration, but not the proliferation, of dermal fibroblasts. NGF induced a remarkable increase in the activity of PI3K/Akt, JNK, ERK, and Rac1, and blockade with their specific inhibitors significantly impaired the NGF-induced migration. In conclusion, NGF significantly accelerated the healing of skin excisional wounds in rats and the fibroblast migration induced by NGF may contribute to this healing process. The activation of PI3K/Akt, Rac1, JNK, and ERK were all involved in the regulation of NGF-induced fibroblast migration.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD / metabolism
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Antigens, Differentiation, Myelomonocytic / metabolism
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Cell Movement / drug effects*
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Cell Proliferation / drug effects
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Cells, Cultured
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Collagen / biosynthesis
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Dermis / pathology
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Epithelium / drug effects
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Epithelium / pathology
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Fibroblasts / drug effects
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Fibroblasts / enzymology
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Fibroblasts / pathology*
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Granulation Tissue / drug effects
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Granulation Tissue / pathology
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Humans
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JNK Mitogen-Activated Protein Kinases / metabolism
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MAP Kinase Signaling System / drug effects*
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Male
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Nerve Growth Factor / administration & dosage
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Nerve Growth Factor / pharmacology*
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Phosphatidylinositol 3-Kinases / metabolism*
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Proliferating Cell Nuclear Antigen / metabolism
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Proto-Oncogene Proteins c-akt / metabolism*
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Rats, Sprague-Dawley
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Transforming Growth Factor beta1 / metabolism
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Up-Regulation / drug effects
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Vascular Endothelial Growth Factor A / metabolism
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Wound Healing / drug effects*
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rac1 GTP-Binding Protein / metabolism
Substances
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Antigens, CD
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Antigens, Differentiation, Myelomonocytic
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CD68 antigen, human
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Proliferating Cell Nuclear Antigen
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Transforming Growth Factor beta1
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Vascular Endothelial Growth Factor A
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Collagen
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Nerve Growth Factor
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Phosphatidylinositol 3-Kinases
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Proto-Oncogene Proteins c-akt
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Extracellular Signal-Regulated MAP Kinases
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JNK Mitogen-Activated Protein Kinases
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rac1 GTP-Binding Protein