Fibrogenesis - IV. Fibrosis and inflammatory bowel disease: cellular mediators and animal models

The cellular mediators of intestinal fibrosis and the relationship between fibrosis and normal repair are not understood. Identification of the types of intestinal mesenchymal cells that produce collagen during normal healing and fibrosis is vital for elucidating the answers to these questions. Acut e injury may cause normal mesenchymal cells to convert to a fibrogenic phen otype that is not maintained during normal healing but may lead to fibrosis when inappropriately sustained. Proliferation of normal or fibrogenic mese nchymal cells may lead to muscularis overgrowth associated with fibrosis. T he presence of increased numbers of vimentin-positive cells within fibrotic , hypertrophied muscularis in Crohn's disease suggests that changes in mese nchymal cell phenotype and number may indeed be associated with fibrosis. F ibrosis is induced in rats by peptidoglycan polysaccharides or trinitrobenz ene sulfonic acid-ethanol administration, but inducing fibrosis in mice has been technically challenging. The development of current mouse models of c olitis, such as dextran sodium sulfate or trinitrobenzene sulfonic acid-eth anol administration, into models of fibrosis will allow us to use genetic m anipulation to study molecular mediators of fibrosis.