title: Collagen type I is not under autocrine control by transforming growth factor-beta 1 in normal and scleroderma fibroblasts.
abstract: BACKGROUND
  The ability of transforming growth factor-beta (TGF-beta) to induce synthesis of extracellular matrix proteins stimulated this study in which we address the hypothesis that TGF-beta can induce, in normal fibroblasts, the sustained, elevated collagen synthesis characteristic of the scleroderma fibroblast.
  
  
  METHODS
  Fibroblasts were studied for synthesis of and responsiveness to TGF-beta. Secreted TGF-beta levels were determined in a bioassay and at the transcriptional level in a series of scleroderma (SSc) and normal fibroblasts. The ability of cells to interact functionally with a 3-dimensional collagen matrix after TGF-beta treatment was examined. The kinetics of TGF-beta-induced fibrosis in fibroblasts was studied.
  
  
  RESULTS
  SSc fibroblasts were not characterized by elevated TGF-beta synthesis. There was no evidence of coordinate regulation of TGF-beta and collagen over passage number. Repeated pulses of 200 pM of TGF-beta did not significantly induce sustained procollagen alpha 1(I) mRNA synthesis in normal fibroblasts, and this treatment did not significantly alter the characteristics of normal fibroblasts in a collagen gel. mRNA for both collagen and TGF-beta type II receptor was induced by TGF-beta in both SSc and control cells. SSc fibroblasts were found to have an impaired ability to activate the small latent complex of TGF-beta.
  
  
  CONCLUSIONS
  Our data give no support to the hypothesis that TGF-beta can maintain the SSc phenotype in vitro or that it is able to induce this phenotype. The inducibility of TGF-beta receptor mRNA in SSc fibroblasts after exposure to TGF-beta suggests that the lack of sustained elevation in collagen synthesis is not due to lack of responsiveness by the fibroblasts but is rather a reflection of the transient nature of TGF-beta-induced fibrosis.
authors: Rheumatology Unit, Royal Free Hospital, London, UK.
authors: A
authors: A
authors: McWhirter
authors: P
authors: P
authors: Colosetti
authors: K
authors: K
authors: Rubin
authors: K
authors: K
authors: Miyazono
authors: C
authors: C
authors: Black
mesh_terms: D002455:Cell Division; D002460:Cell Line; D003094:Collagen / Q000096:biosynthesis*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D008297:Male; D011347:Procollagen / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis; D012594:Scleroderma, Localized / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000502:physiology*
chemical_list: D011347:Procollagen; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D003094:Collagen