Expression and regulation of tissue inhibitor of metalloproteinase-1 and matrix metalloproteinases by intestinal myofibroblasts in inflammatory bowel disease
Expression and regulation of tissue inhibitor of metalloproteinase-1 and matrix metalloproteinases by intestinal myofibroblasts in inflammatory bowel disease
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DOI：
10.1016/s0002-9440(10)63931-4
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发表时间：
2003-04-01
影响因子：
6
通讯作者：
Mahida, YR
中科院分区：
文献类型：
--
作者：
McKaig, BC;McWilliams, D;Mahida, YR
肠纤维化和狭窄经常发生在克罗恩病，但不是溃疡性结肠炎。我们最近发现，与从正常和溃疡性结肠炎组织中获得的肌成纤维细胞相比，从纤维化克罗恩病粘膜样品中分离的肌成纤维细胞表达的转化生长因子（TGF）-β 3的量显著较低，但TGF-β 2的表达显著较高。我们现在报告，在从纤维化克罗恩病粘膜样品建立的肌成纤维细胞培养物中，与从正常或溃疡性结肠炎组织分离的类似细胞相比，金属蛋白酶组织抑制剂（TIMP）-1的组成型表达显著更高。来自正常粘膜和溃疡性结肠炎或克罗恩病粘膜的肌成纤维细胞也表达基质金属蛋白酶（MMP）-1，MMP-2和MMP-3，但不表达MMP-9。重组（r）TGF-β 1和rTGF-β 2，而不是rTGF-β 3，诱导正常肠肌成纤维细胞TIMP-1的表达。这些研究阐明了一种潜在的机制，通过这种机制，TGF-β亚型的差异表达可能导致细胞外基质的过度沉积和狭窄形成，通过TIMP-1介导的MMP活性抑制。
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)-beta3, but the expression of TGF-beta2 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-beta1 and rTGF-beta2, but not rTGF-beta3, 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.