Differential expression of TGF-beta isoforms by normal and inflammatory bowel disease intestinal myofibroblasts.
Am J Physiol Cell Physiol
; 282(1): C172-82, 2002 Jan.
Article
em En
| MEDLINE
| ID: mdl-11742810
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Colite Ulcerativa
/
Doença de Crohn
/
Fator de Crescimento Transformador beta
/
Fibroblastos
Limite:
Humans
Idioma:
En
Revista:
Am J Physiol Cell Physiol
Assunto da revista:
FISIOLOGIA
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Reino Unido