Expression and regulation of tissue inhibitor of metalloproteinase-1 and matrix metalloproteinases by intestinal myofibroblasts in inflammatory bowel disease.
Intestinal fibrosis and strictures frequently occur in Crohn's disease but not ulcerative colitis. We have recently shown that, compared to myofibroblasts obtained from normal and ulcerative colitis tissue, myofibroblasts isolated from fibrotic Crohn's disease mucosal samples express significantly lower amounts of transforming growth factor (TGF)-beta 3, but the expression of TGF-beta 2 was significantly greater. We now report that in myofibroblast cultures established from fibrotic Crohn's disease mucosal samples there is significantly higher constitutive expression of tissue inhibitor of metalloproteinase (TIMP)-1 compared to similar cells isolated from normal or ulcerative colitis tissue. Myofibroblasts derived from normal mucosa and from mucosa affected by ulcerative colitis or Crohn's disease also expressed matrix metalloproteinase (MMP)-1, MMP-2, and MMP-3 but did not express MMP-9. Recombinant (r) TGF-beta 1 and rTGF-beta 2, but not rTGF-beta 3, induced expression of TIMP-1 in normal intestinal myofibroblasts. These studies illustrate a potential mechanism by which differential expression of isoforms of TGF-beta may lead to excessive deposition of extracellular matrix and stricture formation via TIMP-1-mediated inhibition of MMP activity.
McKaig
Brian C
BC
Division of Gastroenterology, University Hospital, Queen's Medical Centre, Nottingham, United Kingdom. dr.mckaig@rwh-tr.nhs.uk
McWilliams
Daniel
D
Watson
Sue A
SA
Mahida
Yashwant R
YR
D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D003424:Crohn Disease / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D005347:Fibroblasts / Q000201:enzymology / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology* / Q000473:pathology; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics*; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D012333:RNA, Messenger; D011994:Recombinant Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1