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Am J Physiol Cell Physiol (September 5, 2001). doi:10.1152/ajpcell.00048.2001
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Articles in PresS, published online ahead of print September 5, 2001
Am J Physiol Cell Physiol, 10.1152/ajpcell.00048.2001
Submitted on February 1, 2001
Accepted on August 22, 2001

Differential expression of transforming growth factor ß isoforms by normal,

B. C McKaig1, K. Hughes1, P. J Tighe2, and Y. R Mahida1*

1 Gastroenterology, University Hospital, Nottingham, United Kingdom
2 Immunology, University Hospital, Nottingham, United Kingdom

* To whom correspondence should be addressed. E-mail: Yash.Mahida{at}nottingham.ac.uk.

Intestinal strictures are frequent in Crohn's disease but not ulcerative colitis. We have investigated the expression of TGF-ß isoforms by primary human intestinal myofibroblasts and the responsiveness of these cells and intestinal epithelial cells to TGF-ß isoforms. Normal intestinal myofibroblasts released predominantly TGF-ß3, ulcerative colitis myofibroblasts expressed both TGF-ß1 and TGF-ß3 whereas in myofibroblast cultures from fibrotic Crohn's disease tissue, there was significantly lower expression of TGF-ß3 but enhanced release of TGF-ß2. Proliferation of Crohn's disease myofibroblasts was significantly greater than that of myofibroblasts derived from normal and ulcerative colitis tissue. Neutralization of the three TGF-ß isoforms did not affect the proliferation of normal and ulcerative colitis intestinal myofibroblasts. Studies on the effect of recombinant TGF-ß isoforms on epithelial restitution and proliferation suggest that TGF-ß2 may be the least effective of the three isoforms in intestinal wound repair. In conclusion, the enhanced release of TGF-ß2, but reduced expression of TGF-ß3, by fibrotic Crohn's disease intestinal myofibroblasts, together with their enhanced proliferative capacity may be of major importance in the development of intestinal strictures.




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