Enhancement of fibroblast collagen synthesis by nitric oxide

Maria B. Witte, Frank J. Thornton, David Thomas Efron, Adrian Barbul

Research output: Contribution to journalArticle

Abstract

Fibroblasts can be stimulated by cytokines to synthesize nitric oxide (NO, nitrogen monoxide), while wound-derived fibroblasts synthesize NO spontaneously. Since wound fibroblasts are phenotypically characterized by greater collagen synthesis when compared to fibroblasts derived from noninjured tissue, we hypothesized that there may be a correlation between wound-induced NO synthesis and enhanced collagen production. To study the role of NO on collagen metabolism, normal dermal fibroblasts were cultured in the presence or absence of the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) and their collagen metabolism was studied on the transcriptional as well as translational level. Fibroblast collagen synthesis was enhanced by 74.3 ± 18.2 and 87.5 ± 28.2% in the presence of 100 and 460 μM SNAP, respectively. This effect was not due to increased collagen type I or type III gene transcription. Cellular proliferation measured by thymidine incorporation was significantly decreased in the presence of SNAP, indicating that the increased collagen production was due to a net increase of collagen synthesis by the cells. Investigation of the collagen breakdown pathway showed that neither collagenase gene expression nor collagenase protein expression was affected by SNAP. The results of this study demonstrate for the first time that NO enhances collagen synthesis, most likely at a post-translational level.

Original languageEnglish (US)
Pages (from-to)572-582
Number of pages11
JournalNitric Oxide - Biology and Chemistry
Volume4
Issue number6
DOIs
StatePublished - 2000

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Keywords

  • Collagen synthesis
  • Fibroblast
  • Nitric oxide

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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