title: NGF accelerates cutaneous wound healing by promoting the migration of dermal fibroblasts via the PI3K/Akt-Rac1-JNK and ERK pathways.
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.
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliate Hospital, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Ji-Cai
authors.initials: JC
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Bei-Bei
authors.initials: BB
authors.lastname: Lin
authors.affiliation: School of Pharmacy, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Hou-Wen
authors.initials: HW
authors.lastname: Hu
authors.affiliation: Wound Treatment Center, The First Affiliate Hospital, Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Cai
authors.initials: C
authors.lastname: Lin
authors.affiliation: Emergency Department, Taizhou Hospital, Wenzhou Medical University, Taizhou 318000, China.
authors.forename: Wen-Yang
authors.initials: WY
authors.lastname: Jin
authors.affiliation: Emergency Department, Taizhou Hospital, Wenzhou Medical University, Taizhou 318000, China.
authors.forename: Fa-Biao
authors.initials: FB
authors.lastname: Zhang
authors.affiliation: Emergency Department, Taizhou Hospital, Wenzhou Medical University, Taizhou 318000, China.
authors.forename: Yan-An
authors.initials: YA
authors.lastname: Zhu
authors.affiliation: Wound Treatment Center, The First Affiliate Hospital, Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Cai-Jiao
authors.initials: CJ
authors.lastname: Lu
authors.affiliation: Translation Medicine Research Center, Cixi People's Hospital, Wenzhou Medical University, Ningbo 315300, China.
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: Wei
authors.affiliation: Departmant of Pharmacy, The Second Affiliate Hospital, Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Rui-Jie
authors.initials: RJ
authors.lastname: Chen
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D020405:Dermis / Q000473:pathology; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D006097:Granulation Tissue / Q000187:drug effects / Q000473:pathology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D020932:Nerve Growth Factor / Q000008:administration & dosage / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D003094:Collagen; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020932:Nerve Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D018809:Proliferating Cell Nuclear Antigen; D051057:Proto-Oncogene Proteins c-akt; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D020830:rac1 GTP-Binding Protein; C067980:CD68 antigen, human; D000097382:CD68 Molecule