2018 Fiscal Year Final Research Report
Innate immunity-mediated regulation of aging and carcinogenesis in the stomach
| Project/Area Number |
16K09278
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Tohoku University |
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Principal Investigator |
ASANO NAOKI 東北大学, 医学系研究科, 講師 (20526454)
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| Research Collaborator |
STROBER Warren
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 上部消化管 / 自然免疫 / 老化 |
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| Outline of Final Research Achievements |
The stomachs of mice deficient in the innate immunity-related molecule NOD1 displayed gastric mucosal atrophy, the precancerous change of gastric cancer. Microarray analysis of the RNA extracted from the stomachs of NOD1-deficient and NOD1-intact mice revealed that the expression of genes related to acid secretion was suppressed in NOD1-deficient mice. NOD1-deficiency led to fewer gastric organoid formation. Furthermore, NOD1-deficient gastric organoids expressed less Atp4a and Pgc, while the expression of Lgr5 and Muc5ac was not altered by the presence of the absence of NOD1. These findings suggested that NOD1 has an influence on the differentiation of gastric stem cells, and its deficiency leads to precancerous changes of gastric cancer.
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| Free Research Field |
消化器内科
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| Academic Significance and Societal Importance of the Research Achievements |
胃発癌の主な病因はHelicobacter pylori (H. pylori)感染であると考えられているが、一方でH. pylori陰性胃癌やH. pylori除菌後胃癌の報告も増加している。自然免疫関連分子NOD1はH. pyloriの排除に重要な役割を果たしていることが知られているが、本研究により、H. pylori非感染下でも、胃の前癌病変の出現に関与していることが判明した。今後、NOD1を活性化を通して前癌病変の出現を抑制することにより、H. pylori陰性胃癌やH. pylori除菌後胃癌の発生を抑制できる可能性が期待される。
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