Roles of Reg protein in the pathophysiology of ulcerative colitis
| Project/Area Number |
17590635
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Dokkyo Medical University |
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Principal Investigator |
FUKUI Hirokazu Dokkyo Medical University, Pathology, Associate Professor, 医学部, 講師 (60378742)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | ulcerative colitis / Reg / carcinogenesis / mucosal regeneration |
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| Research Abstract |
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.
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Report
(3 results)
Research Products
(32 results)
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[Journal Article] Human papillomavirus infection is involved in the development of colonic squamous cell dysplasia in ulcerative colitis-associated carcinogenesis2007
Author(s)
Yoshitake N, Fukui H, Fujii S, Mukawa K, Tominaga K, Sekikawa A, Tomita S, Ichikawa K, Imura J, Nakajima K, Nezu R, Yamada Y, Yoshihara H, Hiraishi H, Fujimori T.
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Journal Title
Inflam Bowel Dis (in press)
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Gastric mucosal hyperplasia via up-regulation of gastrin, induced by persistent activation of gastric innate immunity in MHC class II-deficient mice2006
Author(s)
Fukui T, Nishio A, Okazaki K, Uza N, Ueno S, Kido M, Inoue S, Kitamura H, Kiriya K, Ohashi S, Asada M, Tamaki H, Matsuura M, Kawasaki K, Suzuki K, Uchida K, Fukui H, Nakase H, Watanabe N, Chiba T.
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Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Hypoxia induced by benign intestinal epithelial cells is associated with cydooxygenase-2 expression in stromal cells through AP-1-dependent pathway2006
Author(s)
Uenoyama Y, Seno H, Fukuda A, Sekikawa A, Nanakin A, Sawabu T, Kawada M, Kanda N, Suzuki K, Yada N, Fukui H, Chiba T.
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Journal Title
Oncogene 25
Pages: 3277-85
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Possible role of REG la protein in ulcerative colitis and colitic cancer2005
Author(s)
Sekikawa A, Fukui H, Fujii S, Nanakin A, Kanda N, Uenoyama Y, Sawabu T, Hisatsune H, Kusaka T, Ueno S, Nakase H, Seno H, Fujimori T, Chiba T.
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Description
「研究成果報告書概要(欧文)」より
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[Journal Article] REG la protein may function as a trophic and/or anti-apoptotic factor in the development of gastric cancer2005
Author(s)
Sekikawa A, Fukui H, Fujii S, Takeda J, Nanakin A, Hisatsune H, Seno H, Takasawa S, Okamoto H, Fujimori T, Chiba T.
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Journal Title
Gastroenterology 128
Pages: 642-653
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Expression of Reg 1alpha protein in human gastric cancers2004
Author(s)
Fukui H, Fujii S, Takeda J, Kayahara T, Sekikawa A, Nanakin A, Suzuki K, Hisatsune H, Seno H, Sawada M, Fujimori T, Chiba T.
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Journal Title
Digestion 69
Pages: 177-184
Description
「研究成果報告書概要(欧文)」より
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[Book] 日本臨床2005
Author(s)
福井広一
Total Pages
5
Publisher
日本臨床社
Description
「研究成果報告書概要(和文)」より
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