Nerve growth factor displays stimulatory effects on human skin and lung fibroblasts, demonstrating a direct role for this factor in tissue repair

Abstract

Nerve growth factor (NGF) is a polypeptide which, in addition to its effect on nerve cells, is believed to play a role in inflammatory responses and in tissue repair. Because fibroblasts represent the main target and effector cells in these processes, to investigate whether NGF is involved in lung and skin tissue repair, we studied the effect of NGF on fibroblast migration, proliferation, collagen metabolism, modulation into myofibroblasts, and contraction of collagen gel. Both skin and lung fibroblasts were found to produce NGF and to express tyrosine kinase receptor (trkA) under basal conditions, whereas the low-affinity p75 receptor was expressed only after prolonged NGF exposure. NGF significantly induced skin and lung fibroblast migration in an in vitro model of wounded fibroblast and skin migration in Boyden chambers. Nevertheless NGF did not influence either skin or lung fibroblast proliferation, collagen production, or metalloproteinase production or activation. In contrast, culture of both lung and skin fibroblasts with NGF modulated their phenotype into myofibroblasts. Moreover, addition of NGF to both fibroblast types embedded in collagen gel increased their contraction. Fibrotic human lung or skin tissues displayed immunoreactivity for NGF, trkA, and p75. These data show a direct pro-fibrogenic effect of NGF on skin and lung fibroblasts and therefore indicate a role for NGF in tissue repair and fibrosis.fibrosis ͉ migration ͉ trkA ͉ p75 ͉ gel contraction

Neurotrophin receptor p75NTR characterizes human esophageal keratinocyte stem cells in vitro

“…However, its function in epithelial keratinocytes has not yet been elucidated. Nerve growth factor (NGF) is synthesized and released by human keratinocytes and also by epidermal fibroblasts (Pincelli and Marconi, 2000;Micera et al, 2001). Based on the previous study that both the p75 NTR and the high-affinity NGF receptor (trk) are involved in catagen-anagen control of hair follicle keratinocytes (Botchkarev et al, 2000), it is possible that p75 NTR are also involved in cell fate control for epithelial keratinocyte stem cells through cell-cell interactions including epithelial-mesenchymal interactions.…”

Microarray analysis reveals differential gene expression patterns and regulation of single target genes contributing to the opposing phenotype of TrkA- and TrkB-expressing neuroblastomas

“…(2) Critical elements of the Trk signaling pathway may vary between different tissues leading to a cell-type-specific response. For example, stimulation of TrkA by its specific ligand, nerve growth factor (NGF), leads to differentiation of neurons and neuroblastoma cells, whereas it induces proliferation of fibroblasts and apoptosis of medulloblastoma cells (Muragaki et al, 1997;Micera et al, 2001). In contrast to its role in neuroblastoma, TrkB is associated with a favorable biology and good prognosis in medullary thyroid carcinoma (McGregor et al, 1999), suggesting the response to Trk activation in tumor cells to be cell type specific.…”

IL-4 Downregulates IL-1β and IL-6 and Induces GATA3 in Psoriatic Epidermal Cells: Route of Action of a Th2 Cytokine

“…However, IL-4 significantly reduced NGF in whole PP biopsies ex vivo, probably via inhibition of IL-1b. This suggests additional inhibition by IL-4 of NGF producing dermal cells including DC, macrophages, and fibroblasts (50).…”