Increased collagen type III synthesis by fibroblasts isolated from strictures of patients with Crohn's disease.
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.
Stallmach
A
A
Freie Universität Berlin, Klinikum Steglitz, Germany.
Schuppan
D
D
Riese
H H
HH
Matthes
H
H
Riecken
E O
EO
D000328:Adult; D002448:Cell Adhesion; D002455:Cell Division; D002478:Cells, Cultured; D003094:Collagen / Q000032:analysis / Q000096:biosynthesis*; D003424:Crohn Disease / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011347:Procollagen / Q000096:biosynthesis; D014176:Protein Biosynthesis
D016207:Cytokines; D011347:Procollagen; D003094:Collagen