Analysis of cellular differentiation and involving genes in the mucosal regenerative system of the alimentary tract

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【Purpose and Methods】 Aimed at the collection of basic information which is helpful for the application to regeneration medicine, we examined the cellular differentiation of the regenerative mucosa in the inflammatory bowel disease (IBD). Formalin-fixed, paraffin embedded tissues of surgically resected samples [Crohn's disease: 20 cases (small intestine (15), large intestine (5)), ulcerative colitis: 12 cases] were immunohistochemically investigated using phenotypic markers, such as gastric (MUC5AC, MUC6, HGM, HIK1083) and intestinal (MUC2, Expression of transcriptional factor Cdx-2 was also examined.Results and Discussion】 1. In the cases of Crohn's disease, gastric phenotypic differentiation was observed in 14/15 (93%) of small intestine and 5/5 (100%) of large intestine. 11/15 (73%) of small intestine and 5/5 (100%) of large intestine showed foveolar cell phenotype, while 14/15 (93%) of small intestine and 2/5 (40%) of large intestine revealed pyloric gland cell phenotype. 2. In the … More cases of ulcerative colitis, apparent differentiation to the gastric foveolar cell type was found in 8/12 (75%), although only one case (1/5, 8.3%) showed differentiation to pyloric gland cell type. 3. Expression of Cdx-2, which was essential for the intestinal cell differentiation, was well preserved in all cases of both Crohn's disease and ulcerative colitis. 4. Investigation for other transcriptional factors such as Sox2, Sonic hedgehog (SHH), Musashi-1 was not yet worked well because of the difficulty of the immunohistochemistry. 5. Irrespective of the kind of IBD, regenerative mucosa of small intestine showed a tendency to differentiate to pyloric gland cell type, while that of large intestine foveolar cell type. It should be suggested that the basic information for mucosal structure might be kept even in the disturbed cell differentiation status after the destruction of the mucosa and its structure be controlled by the higher-ranked genes than those involving cell differentiation. Less