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TXNIP expression and mucosal immunity in the epithelium in patients with inflammatory bowel disease

炎症性肠病患者上皮中TXNIP的表达及黏膜免疫

基本信息

批准号：
16591359
负责人：
TAKAHASHI Yasuo
金额：
$ 1.66万
依托单位：
Nihon University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591359/
关键词：
Inflammatory bowel disease TXNIP Ulcerative colitis Gene expression

项目摘要

Ulcerative colitis (UC) is a form of inflammatory bowel disease associated with chronic inflammation and tissue damage of intestine, specifically the large intestine or colon. It is assumed that the oxidative stress that accompanies chronic inflammation contributes to the development of colorectal cancer (CRC) of UC patients. Thioredoxin interacting protein (TXNIP) is a negative regulator of thioredoxin, which is an important regulator of redox balance. TXNIP expression is induced by various types of stress including oxidative stress, and is downregulated in various types of human cancer including colorectal cancer. Previously, we reported that the TXNIP transcript is abundant in terminal differentiated epithelial cells in the colonic mucosa and in lymphocytes in the lymphoid follicles (14). However, TXNIP expression in clinical specimens of UC remains unclear. In this study, using TaqMan RT-PCR assay, we demonstrated that TXNIP expression in UC and CRC colonic mucosa specimens was significantly lower than that in normal tissues. In addition, in situ hybridization study showed that inflammatory cells expressing the TXNIP transcript were abundant in lymphoid follicles, the lamina propria and submucosa in the colonic mucosa of UC patients, but not in epithelial cells at the flat surface. Our results suggest that downregulation of TXNIP may be involved in the pathogenesis of UC, including inflammation and colitis associated colon carcinogenesis.

溃疡性结肠炎（UC）是一种炎症性肠病，与肠道，特别是大肠或结肠的慢性炎症和组织损伤有关。据推测，伴随慢性炎症的氧化应激有助于UC患者结直肠癌（CRC）的发展。硫氧还蛋白相互作用蛋白（TXNIP）是硫氧还蛋白的负调控因子，而硫氧还蛋白是氧化还原平衡的重要调节因子。TXNIP的表达可受包括氧化应激在内的多种应激诱导，并在包括结直肠癌在内的多种人类癌症中下调。先前，我们报道了在结肠黏膜终末分化上皮细胞和淋巴滤泡淋巴细胞中大量存在TXNIP转录本（14）。然而，TXNIP在UC临床标本中的表达尚不清楚。本研究通过TaqMan RT-PCR检测，证实了TXNIP在UC和CRC结肠粘膜标本中的表达明显低于正常组织。此外，原位杂交研究表明，表达TXNIP转录物的炎症细胞在UC患者结肠粘膜的淋巴样滤泡、固有层和粘膜下层中大量存在，而在平坦表面的上皮细胞中则不存在。我们的研究结果表明，TXNIP的下调可能参与UC的发病机制，包括炎症和结肠炎相关的结肠癌发生。