Innate immunity-mediated regulation of aging and carcinogenesis in the stomach

Research Project

Project/Area Number	16K09278
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Gastroenterology
Research Institution	Tohoku University
Principal Investigator	ASANO NAOKI 東北大学, 医学系研究科, 講師 (20526454)
Research Collaborator	STROBER Warren
Project Period (FY)	2016-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000) Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000) Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords	上部消化管 / 自然免疫 / 老化 / NOD1 / 胃粘膜萎縮
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.
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。