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isoforms by
normal and inflammatory bowel disease intestinal myofibroblasts
Divisions of 1 Gastroenterology and 2 Immunology, University Hospital, Nottingham NG7 2UH, United Kingdom
First published
September 5, 2001; 10.1152/ajpcell. 00048.2001.
Intestinal
strictures are frequent in Crohn's disease but not ulcerative colitis.
We investigated the expression of transforming growth factor (TGF)-
isoforms by isolated and cultured primary human intestinal
myofibroblasts and the responsiveness of these cells and intestinal
epithelial cells to TGF- isoforms. Normal intestinal myofibroblasts
released predominantly TGF-3 and ulcerative colitis
myofibroblasts expressed both TGF-1 and
TGF-3, whereas in myofibroblast cultures from fibrotic
Crohn's disease tissue, there was significantly lower expression of
TGF-3 but enhanced release of TGF-2.
These distinctive patterns of TGF- 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- isoforms did not affect the
proliferation of Crohn's disease intestinal myofibroblasts. Studies on
the effect of recombinant TGF- isoforms on epithelial restitution
and proliferation suggest that TGF-2 may be the least effective of the three isoforms in intestinal wound repair. In conclusion, the enhanced release of TGF-2 but reduced
expression of TGF-3 by Crohn's disease intestinal
myofibroblasts, together with their enhanced proliferative capacity,
may lead to the development of intestinal strictures.
fibrosis; wound repair
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