TGF-β3 stimulates and regulates collagen synthesis through TGF-β1-dependent and independent mechanisms

Hiroshi Murata, Linda Zhou, Sofia Ochoa, Anthony Hasan, Evangelos Badiavas, Vincent Falanga

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

In contrast to the TGF-β1 and β2 isoforms, TGF-β3 has shown the ability to downregulate scarring and fibrosis in vivo under certain experimental conditions. In this study, we determined the direct effects of TGF-β3 on cultures of human dermal fibroblasts. TGF-β3 (0.1 to 100 pg per ml) increased DNA synthesis up to 50% (p < 0.01, r = 0.970), collagen protein synthesis up to 200% (dose range of 0.1 to 5 ng per ml, p < 0.001, r = 0.990), and increased α1(I) procollagen mRNA levels (r = 0.999), with maximal effects (200% of control) observed by 24 h. Collagen lattice contraction was increased by more than 50% in response to TGF-β3 (p < 0.001), and to a similar extent as the TGF-β1 isoform. Stimulation of collagen synthesis and of α1(I) procollagen mRNA levels in response to TGF-β3 was partially blocked by a TGF-β1-specific anti-sense oligonucleotide but was still detectable (35% greater than baseline) when TGF-β3 was added to dermal fibroblasts from TGF-β1 knock-out mice. In contrast with these stimulatory effects, however, downregulation of α1(I) procollagen, α1(III) procollagen, and TGF-β1 mRNA levels toward baseline occurred when TGF-β3 (0.1 to 5 ng per ml) was added simultaneously and in combination with TGF-β1. We conclude that stimulation of collagen synthesis by TGF-β3 occurs through TGF-β1-dependent and independent pathways. By downregulating the response to TGF-β1 and by shifting from one pathway to the other, TGF-β3 can dampen and provide fine-tuning to the overall TGF-β's induced program of collagen deposition.

Original languageEnglish (US)
Pages (from-to)258-262
Number of pages5
JournalJournal of Investigative Dermatology
Volume108
Issue number3
DOIs
StatePublished - Jan 1 1997

Keywords

  • fibroblasts
  • fibrosis
  • isoforms
  • scarring

ASJC Scopus subject areas

  • Dermatology

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