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）是与慢性炎症和肠道损伤有关的炎症性肠病的一种形式，特别是大肠或结肠。假定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节剂，硫氧还蛋白是氧化还原平衡的重要调节剂。 TXNIP表达是由包括氧化应激（包括氧化应激）的各种压力诱导的，并在包括大肠癌在内的各种类型的人类癌症中被下调。以前，我们报道了TXNIP转录本在结肠粘膜中的末端分化上皮细胞和淋巴卵泡中的淋巴细胞中很丰富（14）。但是，UC临床标本中的TxNIP表达尚不清楚。在这项研究中，使用Taqman RT-PCR分析，我们证明了UC和CRC结肠粘膜标本中的TxNIP表达明显低于正常组织中的TxNIP。此外，原位杂交研究表明，表达TXNIP转录本的炎性细胞在UC患者的结肠粘膜中淋巴卵泡，固有层和粘膜粘膜中丰富，但在平坦表面的上皮细胞中却不多。我们的结果表明，TXNIP的下调可能与UC的发病机理有关，包括炎症和结肠炎相关的结肠癌发生。