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CHARACTERIZATION OF SMOOTH MUSCLE CELL PHENOTYPE IN INTESTINAL STRICTURES FROM THE TNBS RAT MODEL OF COLITIS

SL Marlow, M Blennerhassett
GIDRU and Department of Biology, Queen's University, Kingston, Ontario

BACKGROUND: Intestinal strictures are areas of thickened, noncompliant tissue found at sites of inflammation, and can lead to potentially life threatening consequences in Crohn's disease. We have previously found that strictures occur sporadically in the TNBS rat model of colitis and that the resulting strictured tissues have a loss of innervation, as well as thickening and disorganization of the smooth muscle layers. Histochemistry showed that extracellular matrix collagen increased, however, cellular structures still predominated in the strictured region.
HYPOTHESIS: Phenotypic alteration of intestinal smooth muscle cells (ISMC) during inflammation contribute to the formation of intestinal strictures.
METHODS: Histological staining and immunocytochemistry were used to characterize the cellular and extracellular composition of strictured tissues in vivo. Incorporation of BrDU for 3 h in vivo and subsequent immunocytochemistry was used to assess ISMC hyperplasia. ISMC phenotype was studied in tissue culture using the method of Wells et al (2004).
RESULTS: Immunolabelling and stereological analysis showed an increase in the total number of a-smooth muscle actin-positive ISMC in strictures relative to adjacent regions. While ISMC from nonstrictured regions expressed the intermediate filaments desmin but not vimentin, ISMC from strictures showed a myofibroblast-like phenotype (desmin-negative, vimentin-positive). Further, BrDU incorporation into a-smooth muscle actin-positive cells was evident throughout the strictured region. While primary cultures of ISMC maintained the in vivo phenotype, the onset of mitogenic responsiveness was associated with dedifferentiation and the acquisition of vimentin reactivity.
CONCLUSIONS: Intestinal strictures are predominantly cellular. ISMC from strictured tissue show evidence of dedifferentiation and continued proliferation. Prolonged ISMC hyperplasia may result in the altered phenotype associated with stricture formation.
Supported by the Crohn's and Colitis Foundation of Canada

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