Stallmach A, Schuppan D, Riese H H, Matthes H, Riecken E O
Freie Universität Berlin, Klinikum Steglitz, Germany.
Gastroenterology. 1992 Jun;102(6):1920-9. doi: 10.1016/0016-5085(92)90314-o.
Increased type III collagen deposition in all layers of the intestinal tract, including the lamina propria, is a common feature of strictures in Crohn's disease. In the present study, it was found that in comparison with fibroblasts from normal or nonstrictured but inflamed intestinal lamina propria, the fibroblasts isolated from strictures of patients with Crohn's disease produce significantly more collagen, especially collagen type III. Transforming growth factor beta 1 (TGF-beta 1) significantly increased collagen type III synthesis in intestinal lamina propria fibroblasts isolated from all patients. The effect of TGF-beta 1 on type III collagen synthesis in fibroblasts from strictures in Crohn's disease was significantly higher than that in fibroblasts from inflamed specimens of the same patients. In contrast, platelet-derived growth factor decreased collagen type III synthesis in lamina propria fibroblasts derived from strictures compared with fibroblasts from nonstrictured but inflamed tissue. These findings indicate that fibroblasts in the lamina propria of patients with Crohn's disease have a different reactivity towards cytokines. On the basis of increased type III collagen deposition in intestinal strictures of Crohn's disease by using cell adhesion and cell proliferation assays, it was shown that collagen type III stimulated adhesion and proliferation of lamina propria fibroblasts. The current data provide evidence that the different reactivity of mesenchymal cells to cytokines in terms of synthesizing type III collagen fibrils, which is a major component of collagen fibrils, may play an important role in the pathogenesis of fibrosis and stricture formation in chronic inflammatory bowel diseases.
包括固有层在内的肠道各层中III型胶原蛋白沉积增加是克罗恩病狭窄的一个常见特征。在本研究中，发现与来自正常或无狭窄但发炎的肠道固有层的成纤维细胞相比，从克罗恩病患者狭窄部位分离出的成纤维细胞产生的胶原蛋白显著更多，尤其是III型胶原蛋白。转化生长因子β1（TGF-β1）显著增加了从所有患者分离出的肠道固有层成纤维细胞中III型胶原蛋白的合成。TGF-β1对克罗恩病狭窄部位成纤维细胞中III型胶原蛋白合成的影响显著高于对同一患者发炎标本中成纤维细胞的影响。相比之下，与来自无狭窄但发炎组织的成纤维细胞相比，血小板衍生生长因子降低了狭窄部位固有层成纤维细胞中III型胶原蛋白的合成。这些发现表明，克罗恩病患者固有层中的成纤维细胞对细胞因子具有不同的反应性。通过细胞黏附和细胞增殖试验，基于克罗恩病肠道狭窄中III型胶原蛋白沉积增加的现象，研究表明III型胶原蛋白刺激了固有层成纤维细胞的黏附和增殖。目前的数据提供了证据，即间充质细胞在合成作为胶原纤维主要成分的III型胶原纤维方面对细胞因子的不同反应性，可能在慢性炎症性肠病的纤维化和狭窄形成的发病机制中起重要作用。
