科学研究費助成事業　　研究成果報告書

様　式　Ｃ－１９、Ｆ－１９、Ｚ－１９ （共通）

機関番号：

研究種目：

課題番号：

研究課題名（和文）

研究代表者

研究課題名（英文）

交付決定額（研究期間全体）：（直接経費）

１１３０１

基盤研究(C)（一般）

2015～2013

胃における自然免疫応答が前癌病変発生を制御する機序の解明

Innate immunity-mediated regulation on the induction of precancerous lesions in the stomach.

２０５２６４５４研究者番号：

浅野　直喜（Asano, Naoki）

東北大学・大学病院・助教

研究期間：

２５４６０９２５

平成 年 月 日現在２８ ５ ２４

円 3,900,000

研究成果の概要（和文）：自然免疫関連分子NOD1はその下流分子であるTRAF3を介して、Helicobacter pylori (H. pylori)感染による胃粘膜上皮におけるCdx2やMuc2の誘導発現、NF-κB p65の活性化を抑制していた。反対に、ATP4aに関しては、NOD1はその発現維持に寄与していた。H. pylori感染による遺伝子発現の変化はNOD1ノックアウト(KO)マウスの胃における腸上皮化生や胃粘膜萎縮といった前癌病変の発生として現れた。NOD1KOマウスの胃におけるTRAF3の発現は野生型マウスのそれより有意に低く、胃前癌病変発生の一因となっている可能性が示唆された。

研究成果の概要（英文）：Innate immunity-related molecule NOD1 suppressed Helicobacter pylori (H. pylori) infection induced Cdx2 and Muc2 induction and NF-κB p65 activation in gastric epithelial cells. On the other hand, NOD1 was required for the maintenance of ATP4a expression. The changes in gene expression upon H. pylori infection were observed as induction of intestinal metaplasia and gastric mucosal atrophy in the stomachs of H. pylori-infected NOD1-deficient mice 12 months after infection. The expression of TRAF3 was lower in these mice compared to NOD1-intact mice and this could be one of the causes for the induction of precancerous lesions in H. pylori-infected stomach.

研究分野： 消化器内科

キーワード： NOD1　Helicobacter pylori

１版

H. pylori (Helicobacter pylori)

H. pylori

(Iijima K et al: Tohoku J Exp Med, 2012)

Cdx2(Sakamoto H et al: Scand J

Gastroenterol, 2010) Cdx2

Sox2

(Asonuma S, Imatani A, Asano N et al: Am J Physiol Gastrointest Liver Physiol, 2009)

H. pylori

NOD1 (Nucleotide-binding

Oligomerization Domain 1) PGN (peptidoglycan)

Toll

H. pylori �

H. pyloriCagA PGN

CagA NF-κB(Proc Natl Acad Sci,2005;

EMBO,2009) PGNNOD1 NF-κB

(Viala J et al: Nat Immunol, 2004)

H. pyloriNOD1 NF-κB

(Watanabe T, Asano N et al: J Clin Invest, 2010)

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RNACdx2

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ATP4a RT-PCR

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Warren Strober Cdx2

expression and intestinal metaplasia induced by H. pylori infection of gastric cells is regulated by NOD1-mediated innate immune responses Cancer Research 76 20161135-1145 doi: 10.1158/0008-5472.CAN-15-2272

1

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