Differential expression of TGF-β isoforms by normal and inflammatory bowel disease intestinal myofibroblasts

被引:130
作者
McKaig, BC
Hughes, K
Tighe, PJ
Mahida, YR [1 ]
机构
[1] Univ Nottingham Hosp, Div Gastroenterol, Nottingham NG7 2UH, England
[2] Univ Nottingham Hosp, Div Immunol, Nottingham NG7 2UH, England
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2002年 / 282卷 / 01期
关键词
fibrosis; wound repair;
D O I
10.1152/ajpcell.00048.2001
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Intestinal strictures are frequent in Crohn's disease but not ulcerative colitis. We investigated the expression of transforming growth factor (TGF)-beta isoforms by isolated and cultured primary human intestinal myofibroblasts and the responsiveness of these cells and intestinal epithelial cells to TGF-beta isoforms. Normal intestinal myofibroblasts released predominantly TGF-beta (3) and ulcerative colitis myofibroblasts expressed both TGF-beta (1) and TGF-beta (3), whereas in myofibroblast cultures from fibrotic Crohn's disease tissue, there was significantly lower expression of TGF-beta (3) but enhanced release of TGF- beta (2). These distinctive patterns of TGF-beta isoform release were sustained through several myofibroblast passages. Proliferation of Crohn's disease myofibroblasts was significantly greater than that of myofibroblasts derived from normal and ulcerative colitis tissue. In contrast to cells from normal and ulcerative colitis tissue, neutralization of the three TGF-beta isoforms did not affect the proliferation of Crohn's disease intestinal myofibroblasts. Studies on the effect of recombinant TGF-beta isoforms on epithelial restitution and proliferation suggest that TGF- beta (2) may be the least effective of the three isoforms in intestinal wound repair. In conclusion, the enhanced release of TGF- beta (2) but reduced expression of TGF-beta (3) by Crohn's disease intestinal myofibroblasts, together with their enhanced proliferative capacity, may lead to the development of intestinal strictures.
引用
收藏
页码:C172 / C182
页数:11
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