Growth regulation in scleroderma fibroblasts: increased response to transforming growth factor-beta 1

J Invest Dermatol. 1995 Jul;105(1):128-32. doi: 10.1111/1523-1747.ep12313452.


We investigated the responses of normal and scleroderma fibroblasts to various growth factors, especially transforming growth factor-beta 1 (TGF-beta 1). The effects of various growth factors on [3H]thymidine incorporation in normal and scleroderma fibroblasts were examined. [125I]-labeled platelet-derived growth factor (PDGF)-BB binding in scleroderma and normal fibroblasts was examined both in the presence and absence of TGF-beta 1 (1 ng/ml). Cytoplasmic protein was isolated and analyzed by Western blotting. Total RNA from fibroblasts was also isolated and analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) using specific primer sets. Mitogenic responses to TGF-beta 1 (0.33-1 ng/ml) in seven scleroderma fibroblast strains were significantly greater than those in normal controls. [125I]-PDGF-BB binding to scleroderma fibroblasts was increased after TGF-beta 1 stimulation. The increased response to TGF-beta 1 was shown to be mediated through PDGF-like protein induction; TGF-beta 1-treated scleroderma fibroblasts produced greater amounts of 36-kD PDGF-like protein, which was reported previously as connective tissue growth factor (CTGF), than did TGF-beta 1-treated normal fibroblasts. TGF-beta 1 treatment also upregulated PDGF-alpha receptor expression in scleroderma fibroblasts but not in normal dermal fibroblasts. mRNA expression of CTGF and PDGF-alpha receptor was correlated with the above protein expression. These observations suggest that the increased growth response to TGF-beta 1 in scleroderma fibroblasts is mediated through the induction of CTGF and PDGF-alpha receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Division / drug effects
  • Cells, Cultured
  • Female
  • Fibroblasts / drug effects
  • Humans
  • Platelet-Derived Growth Factor / biosynthesis
  • Receptors, Platelet-Derived Growth Factor / biosynthesis
  • Scleroderma, Systemic / pathology*
  • Transforming Growth Factor beta / pharmacology*


  • Platelet-Derived Growth Factor
  • Transforming Growth Factor beta
  • Receptors, Platelet-Derived Growth Factor