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

Alessandra Micera, Eliana Vigneti, Dalia Pickholtz, Reuven Reich, Orit Pappo, Sergio Bonini, François Xavier Maquart, Luigi Aloe, Francesca Levi-Schaffer

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)6162-6167
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number11
DOIs
Publication statusPublished - May 22 2001

Keywords

  • Fibrosis
  • Gel contraction
  • Migration
  • p75
  • trkA

ASJC Scopus subject areas

  • Genetics
  • General

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