TGF β1 and PDGF AA override Collagen type I inhibition of proliferation in human liver connective tissue cells

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• 作者：Alvaro T Geremias (1)
  Marcelo A Carvalho (2)
  Radovan Borojevic (1) (3)
  Alvaro NA Monteiro (1)
  
• 刊名：BMC Gastroenterology
• 出版年：2004
• 出版时间：December 2004
• 年：2004
• 卷：4
• 期：1
• 全文大小：582KB
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  35. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-230X/4/30/prepub
  
• 作者单位：Alvaro T Geremias (1)
  Marcelo A Carvalho (2)
  Radovan Borojevic (1) (3)
  Alvaro NA Monteiro (1)
  
  1. Departamento de Bioquímica, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21949, Brazil
  2. Laboratório de Metabolismo Macromolecular Firmino Torres de Castro, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941, Brazil
  3. Departamento de Histologia e Embriologia, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941, Brazil
  

文摘

Background A marked expansion of the connective tissue population and an abnormal deposition of extracellular matrix proteins are hallmarks of chronic and acute injuries to liver tissue. Liver connective tissue cells, also called stellate cells, derived from fibrotic liver have been thoroughly characterized and correspond phenotypically to myofibroblasts. They are thought to derive from fat-storing Ito cells in the perisinusoidal space and acquire a contractile phenotype when activated by tissue injury. In the last few years it has become evident that several peptide growth factors such as PDGF AA and TGF-β are involved in the development of fibrosis by modulating myofibroblast proliferation and collagen secretion. The fact that during the development of chronic fibrosis there is concomitant deposition of collagen, a known inhibitory factor, and sustained cell proliferation, raises the possibility that stellate cells from chronic liver fibrosis patients fail to respond to normal physiologic controls. Methods In this study we address whether cells from fibrotic liver patients respond to normal controls of proliferation. We compared cell proliferation of primary human liver connective tissue cells (LCTC) from patients with liver fibrosis and skin fibroblasts (SF) in the presence of collagens type I and IV; TGF-β, PDGF AA and combinations of collagen type I and TGF-β or PDGF AA. Results Our results indicate that despite displaying normal contact and collagen-induced inhibition of proliferation LCTC respond more vigorously to lower concentrations of PDGF AA. In addition, we show that collagen type I synergizes with growth factors to promote mitogenesis of LCTC but not SF. Conclusions The synergistic interaction of growth factors and extracellular matrix proteins may underlie the development of chronic liver fibrosis.