Altered expression of epimorphin in ulcerative colitis.

Abstract

Epimorphin is suggested to play a key role in the morphogenesis of epithelial cells. We focused on epimorphin and attempted to clarify the relationship between expression of this molecule and inflammatory bowel disease (IBD). Colonic specimens were taken from 23 patients with ulcerative colitis (UC), 15 with Crohn's disease (CD), six with non-IBD colitis, and 10 normal controls. Distribution and expression of epimorphin protein were examined by immunohistochemistry and western blot analysis, and expression of epimorphin messenger (m)RNA by reverse transcription-polymerase chain reaction. Distribution of basic fibroblast growth factor (bFGF) was also examined by immunohistochemistry. In the normal colonic mucosa, epimorphin was observed around the epithelial cells, in some fibroblasts, vascular endothelial cells, and macrophages. In UC patients, epimorphin around epithelial cells disappeared or decreased, and the number of epimorphin-containing cells (mean + standard error/mm2) was significantly increased in active UC patients (1550.8 +/- 144.2) compared with patients in remission (692.8 +/- 45.8), CD patients (790.0 +/- 31.2), non-IBD colitis patients (710.8 +/- 29.2), and controls (664.8 +/- 39.6) (P < 0.01). The number of bFGF-containing cells was significantly increased in active UC and CD patients compared with UC patients in remission, CD and non-IBD colitis patients, and controls (P < 0.05 or P < 0.01). Total expression of epimorphin protein and mRNA was increased in the active stage of UC. Expression of the 34 kDa epimorphin isoform decreased or disappeared in 20 out of 23 cases of UC. Our results suggest that altered expression of epimorphin contributes to impaired healing and chronic inflammation in the colonic mucosa of UC patients.