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

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 i n tissue repair. Because fibroblasts represent the main target and effector cells in these processes, to investigate whether NGF is involved in lung a nd skin tissue repair, we studied the effect of NGF on fibroblast migration , proliferation, collagen metabolism, modulation into myofibroblasts, and c ontraction of collagen gel. Both skin and lung fibroblasts were found to pr oduce NGF and to express tyrosine kinase receptor (trkA) under basal condit ions, whereas the low-affinity p75 receptor was expressed only after prolon ged NGF exposure. NGF significantly induced skin and lung fibroblast migrat ion in an in vitro model of wounded fibroblast and skin migration in Boyden chambers. Nevertheless NGF did not influence either skin or lung fibroblas t proliferation, collagen production, or metalloproteinase production or ac tivation. In contrast, culture of both lung and skin fibroblasts with NGF m odulated 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, tr kA, 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.