Dammeier J, Brauchle M, Falk W, Grotendorst G R, Werner S
Max-Planck-Institute für Biochemie, Martinsried, Germany.
Int J Biochem Cell Biol. 1998 Aug;30(8):909-22. doi: 10.1016/s1357-2725(98)00046-6.
Inflammatory bowel disease (IBD) is a multifactorial disorder which is characterized by massive damage of the epithelium and the underlying mesenchyme of the intestine. Due to the potent effect of connective tissue growth factor (CTGF) on fibroblast proliferation and connective tissue deposition we speculated about a possible role of this mitogen in IBD. Here we demonstrate a strikingly increased expression of CTGF mRNA in surgical specimens of patients suffering from two forms of IBD, Crohn's disease and ulcerative colitis. In most specimens, the levels of CTGF mRNA correlated with the degree of inflammation as assessed by histological analysis of adjacent tissue samples and by expression analysis of the pro-inflammatory cytokine interleukin-1 beta. However, areas of little inflammation which were characterized by severe fibrosis also revealed high levels of CTGF mRNA. Expression of transforming growth factor beta-1 (TGF-beta 1), the only known inducer of CTGF so far, as well as of the CTGF target genes collagen I alpha 1, fibronectin and integrin alpha 5 revealed a strong correlation with the expression of CTGF. These data suggest a prominent role of CTGF in the repair of mucosal injury in IBD and in the aberrant deposition of extracellular matrix leading to fibrosis and stenosis, one major complication in IBD, especially in Crohn's disease.
炎症性肠病(IBD)是一种多因素疾病,其特征是肠道上皮和下层间充质的大量损伤。由于结缔组织生长因子(CTGF)对成纤维细胞增殖和结缔组织沉积有强大作用,我们推测这种有丝分裂原在IBD中可能发挥作用。在此,我们证明在患有两种IBD(克罗恩病和溃疡性结肠炎)的患者手术标本中,CTGF mRNA的表达显著增加。在大多数标本中,CTGF mRNA水平与通过相邻组织样本的组织学分析以及促炎细胞因子白细胞介素-1β的表达分析所评估的炎症程度相关。然而,以严重纤维化为特征的轻度炎症区域也显示出高水平的CTGF mRNA。目前唯一已知的CTGF诱导剂转化生长因子β-1(TGF-β1)以及CTGF靶基因胶原蛋白Iα1、纤连蛋白和整合素α5的表达与CTGF的表达密切相关。这些数据表明CTGF在IBD黏膜损伤修复以及导致纤维化和狭窄(IBD尤其是克罗恩病的一种主要并发症)的细胞外基质异常沉积中起重要作用。