title: Palm oil tocotrienol rich fraction reduces extracellular matrix production by inhibiting transforming growth factor-β1 in human intestinal fibroblasts.
abstract: OBJECTIVE
  Extracellular matrix deposition is key event for the development of bowel stenosis in Crohn's disease patients. Transforming growth factor-β plays a key role in this process. We aimed at characterizing the effects of tocotrienol rich fraction on ECM proteins production and molecules that regulate the synthesis and degradation of extracellular matrix, matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1, in human intestinal fibroblasts, and at elucidating whether the effects of tocotrienol rich fraction (TRF) are mediated through inhibition of TGF-β1.
  
  
  METHODS
  HIF were isolated from colonic or ileal tissue from Crohn's disease patients and control subjects, and were treated with TRF from palm oil either alone or in combination with TGF-β1. Procollagen 1, procollagen 3, TIMP-1 and MMP-3 production, and Smad3 phosphorylation were analyzed by Western-blotting.
  
  
  RESULTS
  TRF significantly diminished procollagen 1 and 3 synthesis in HIF. Treatment of HIF with TRF increased MMP-3 production but did not modify TIMP-1. TGF-β1 induced Smad3 phosphorylation and enhanced procollagen 1 and 3 and TIMP-1 production. Pre-treatment of HIF with TRF prevented Smad3 phosphorylation and minimized the increase in collagen 1 and 3 production caused by TGF-β1.
  
  
  CONCLUSIONS
  TRF has anti-fibrogenic effects on HIF, decreasing ECM production and increasing its degradation. This effect is mediated, at least in part, by inhibition of TGF-β1.
authors.affiliation: Department of Gastroenterology, Hospital Clínic i Provincial/IDIBAPS, 170 Villarroel, 08036 Barcelona, CIBER EHD, Catalunya, Spain.
authors.forename: Jeroni
authors.initials: J
authors.lastname: Luna
authors.forename: Maria Carme
authors.initials: MC
authors.lastname: Masamunt
authors.forename: Josep
authors.initials: J
authors.lastname: Llach
authors.forename: Salvadora
authors.initials: S
authors.lastname: Delgado
authors.forename: Miquel
authors.initials: M
authors.lastname: Sans
mesh_terms: D015153:Blotting, Western; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D003424:Crohn Disease / Q000378:metabolism / Q000473:pathology*; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D000073878:Palm Oil; D010938:Plant Oils / Q000494:pharmacology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D024508:Tocotrienols / Q000494:pharmacology; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D010938:Plant Oils; D019715:Tissue Inhibitor of Metalloproteinase-1; D024508:Tocotrienols; D053773:Transforming Growth Factor beta1; D000073878:Palm Oil; D019278:Matrix Metalloproteinase 3