| Project/Area Number |
16590595
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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 | Shimane University |
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Principal Investigator |
KAZUMORI Hideaki Shimane University, School of Medicine, Assistant Professor, 医学部, 助手 (20332786)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIHARA Shunji Shimane University, School of Medicine, Junior Associate Professor, 医学部, 講師 (80263531)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Barrett's esophagus / bile acid / Cdx2 / cholic acid / dehydrocholic acid / CdX2 |
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| Research Abstract |
Background & Aims : The mechanism of transformation to intestinal metaplasia in Barrett's esophagus has not been clarified. We investigated the effects of various bile acids on the expression of Cdx2 in cultured esophageal squamous epithelial cells. In addition, morphological and histochemical changes of squamous cells to intestinal epithelial cells were studied in response to bile acid-induced expression of Cdx2.
Methods : A rat model of Barrett's esophagus was produced by anastomosing the esophagus and jejunum, and Cdx2 expression was investigated by immunohistochemistry. Further, Cdx2 gene expression was studied in cultured esophageal squamous epithelial cells in response to various bile acids, and a Cdx2 promoter luciferase assay with and without mutation was employed. In addition, primary cultured esophageal squamous epithelial cells were transfected with Cdx2 expression vectors and their possible transformation to intestinal type epithelial cells was investigated.
Results : Esophago-jejunal anastomoses formed intestinal goblet cell metaplasia in rat esophagus specimens and the metaplastic epithelium strongly expressed Cdx2. When the effects of 11 kinds of bile acids on the gene expression of Cdx2 were examined, only cholic acid (CA) and dehydrocholic acid (DHCA) dose-dependently increased Cdx2 promoter activity and Cdx2 protein production in cultured esophageal keratinocytes. Mutation analysis results suggested that 2 NF-kB binding sites are responsible for the bile acid-induced activation of the Cdx2 promoter. Further, transfection of the Cdx2 expression vector in cultured rat esophageal keratinocytes induced production of intestinal type mucin, MUC2, in cells that expressed Cdx2.
Conclusions : We showed that CA and DHCA activate Cdx2 promoter via NF-kB, and stimulate the production Cdx2 protein in esophageal keratinocytes with a resulting production of intestinal type mucin.
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