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

溃疡性结肠炎(UC)是一种炎症性肠道疾病，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参与了UC患者结直肠癌的发生发展。硫氧还蛋白相互作用蛋白(TXNIP)是硫氧还蛋白的负性调节因子，是氧化还原平衡的重要调节因子。TXNIP的表达由包括氧化应激在内的各种应激诱导，并在包括结直肠癌在内的各种人类癌症中下调。此前，我们曾报道TXNIP转录本在结肠粘膜的终末分化上皮细胞和淋巴滤泡中的淋巴细胞中大量存在(14)。然而，TXNIP在UC临床标本中的表达尚不清楚。在本研究中，我们用TaqMan RT-PCR方法证明了TXNIP在UC和CRC结肠黏膜组织中的表达显著低于正常组织。此外，原位杂交显示，UC患者结肠黏膜的淋巴滤泡、固有层和粘膜下层均有大量表达TXNIP转录本的炎性细胞，而平面炎性细胞则不表达。我们的结果提示TXNIP的下调可能参与了UC的发病机制，包括炎症和结肠炎相关性结肠癌的发生。

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.