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Roles of Reg protein in the pathophysiology of ulcerative colitis

Reg蛋白在溃疡性结肠炎病理生理学中的作用

基本信息

批准号：
17590635
负责人：
FUKUI Hirokazu
金额：
$ 1.98万
依托单位：
Dokkyo Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590635/
关键词：
ulcerative colitis Reg carcinogenesis mucosal regeneration

项目摘要

Recently, comprehensive analyses using DNA array repeatedly confirmed that Reg family genes are novel genes overexpressed in ulcerative colitis (UC) tissues. In the preset study the level of REG Iα gene expression was found to be much higher in UC mucosa than in normal colonic mucosa and furthermore correlated significantly with severity of inflammation in UC tissues. Moreover, REG Iα protein was strongly expressed not only in UC-associated cancer (colitic cancer) but also in precancerous dysplastic lesions in longstanding UC patients with high risk for cancer development. Regarding the regulatory mechanism for REG Iα gene expression, it was clarified that the element from position -142 and -134 is responsible for IL-6 induced-REG Iα promoter activation and suggested that IL-6/STAT3 signaling is crucial for REG Iα gene expression in cancer cells in vitro. As for the biological functions, we clarified that REG Iα protein acts as a mitogenic and/or an anti-apoptotic factor in UC-colitic cancer sequence and exerts its anti-apoptotic effect by activating Akt/Bcl-2 or Bcl-xL signaling. Thus, REG Iα protein may mediate anti-apoptotic effect of STAT3 signaling. REG IV as well as REG Iα protein was clarified to be overexpressed in UC, precancerous dysplasia and colitic cancer lesions and functioned as a growth-promoting and/or anti-apoptotic factor for colon cancer cells. However, REG IV gene expression was enhanced by basic-fibroblast growth factor and keratinocyte growth factor but not by cytokines stimulation in UC mucosa. In conclusions, REG family proteins act as a growth-promoting and/or anti-apoptosis factor in UC-colitic cancer sequence and its expression is possible to be a useful marker to predict a development of colitic cancer in UC patients.

近年来，DNA芯片技术的研究证实Reg家族基因是溃疡性结肠炎（UC）组织中高表达的新基因。在本研究中，发现REG Iα基因在UC粘膜中的表达水平远高于正常结肠粘膜，并且与UC组织中的炎症严重程度显著相关。此外，REG Iα蛋白不仅在UC相关癌症（结肠癌）中强表达，而且在具有癌症发展高风险的长期UC患者的癌前发育不良病变中也强表达。关于REG Iα基因表达的调控机制，阐明了来自位置-142和-134的元件负责IL-6诱导的REG Iα启动子激活，并表明IL-6/STAT 3信号传导对癌细胞中的REG Iα基因表达至关重要。在生物学功能方面，我们阐明了REG Iα蛋白在UC-结肠癌序列中作为促有丝分裂和/或抗凋亡因子，并通过激活Akt/Bcl-2或Bcl-xL信号传导发挥其抗凋亡作用。因此，REG Iα蛋白可能介导STAT 3信号转导的抗凋亡作用。REG IV和REG Iα蛋白在UC、癌前异型增生和结肠炎癌病变中过表达，并作为结肠癌细胞的促生长和/或抗凋亡因子发挥作用。然而，REG IV基因表达增强碱性成纤维细胞生长因子和角质形成细胞生长因子，但不通过细胞因子刺激UC粘膜。结论：REG家族蛋白在UC-结肠癌序列中起促生长和/或抗凋亡因子的作用，其表达可能是预测UC患者结肠癌发生的有用标志物。

项目成果

期刊论文数量（32）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Expression of Reg 1alpha protein in human gastric cancers

Reg 1α蛋白在人胃癌中的表达

DOI：
发表时间：
2004
期刊：
Digestion 69
影响因子：
0
作者：
Fukui H;Fujii S;Takeda J;Kayahara T;Sekikawa A;Nanakin A;Suzuki K;Hisatsune H;Seno H;Sawada M;Fujimori T;Chiba T.
通讯作者：
Chiba T.

Colonic expression of heme oxygenase-1 is associated with a better long-term survival in patients with colorectal cancer

DOI：
10.1080/00365520701192383
发表时间：
2007-01-01
期刊：
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY
影响因子：
1.9
作者：
Becker, Jan C.;Fukui, Hirokazu;Fujimori, Takahiro
通讯作者：
Fujimori, Takahiro

Nuclear expression of phosphorylated EGFR is associated with poor prognosis of patients with esophageal squamous cell carcinoma.

磷酸化EGFR的核表达与食管鳞状细胞癌患者的不良预后相关。

DOI：
发表时间：
2007
期刊：
Pathobiology 74
影响因子：
0
作者：
Hoshino M;Fukui H;Ono Y;Sekikawa A;Ichikawa K;Tomita S;Imai Y;Imura J;Hiraishi H and Fujimori T.
通讯作者：
Hiraishi H and Fujimori T.

Magnifying pharmaco-endoscopy : response of microvessels to epinephrine stimulation in differentiated early gastric cancers

放大药物内窥镜：分化型早期胃癌中微血管对肾上腺素刺激的反应

DOI：
发表时间：
2006
期刊：
Gastrointest Endosc 64
影响因子：
0
作者：
Jinushi M;Takehara T;Tatsumi T;Yamaguchi S;Sakamori R;Hiramastu N;Kanto T;Ohkawa K;Hayashi N.;Fukui H
通讯作者：
Fukui H

Involvement of cyclooxygenase-2 in gastric mucosal hypertrophy in gastrin transgenic mice.

环氧合酶-2 参与胃泌素转基因小鼠胃粘膜肥大。