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

【目的与方法】研究炎症性肠病（IBD）再生黏膜的细胞分化情况，以期为再生医学的应用提供基础资料。采用胃（MUC5AC、MUC6、HGM、HIK1083）、肠（MUC2）等表型标记物，对手术切除标本进行福尔马林固定、石蜡包埋组织免疫组化研究[克罗恩病20例(小肠15例、大肠5例、溃疡性结肠炎12例]，同时检测转录因子Cdx-2的表达。【结果与讨论】在克罗恩病病例中，14/15（93%）的小肠和5/5（100%）的大肠出现胃表型分化。11/15（73%）的小肠和5/5（100%）的大肠表现为小凹细胞表型，14/15（93%）的小肠和2/5（40%）的大肠表现为幽门腺细胞表型。2. 溃疡性结肠炎有8/12例（75%）向胃小凹细胞型分化，仅有1例（1/5,8.3%）向幽门腺细胞型分化。3. Cdx-2的表达是肠细胞分化所必需的，在克罗恩病和溃疡性结肠炎的所有病例中都得到了很好的保存。4. 由于免疫组化的困难，对其他转录因子如Sox2、Sonic hedgehog （SHH）、Musashi-1的研究尚未很好地进行。5. 无论哪种IBD，小肠再生粘膜均有向幽门腺细胞型分化的趋势，而大肠再生粘膜则有向凹泡细胞型分化的趋势。我们认为，粘膜破坏后，即使在细胞分化受到干扰的状态下，粘膜结构的基本信息也可能被保留下来，其结构受比参与细胞分化的基因更高级的基因控制。少

【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