Functional analysis of autophagy in gastric carcinogenesis and its application to prevention

• Project/Area Number: 17K09348
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: University of Fukui
• Principal Investigator: OHTANI MASAHIRO 福井大学, 学術研究院医学系部門(附属病院部), 講師 (20372500)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: ヘリコバクターピロリ菌 / オートファジー / ヘリコバクターピロリ / ヘリコバクターピロリ感染 / 胃癌

Outline of Final Research Achievements

We investigated the effect of autophagy on inflammatory gastric carcinogenesis caused by Helicobacter pylori (HP) infection. HP-infected gastrin transgenic mice (INS-GAS mice) had histopathologically significant gastritis and dysplasia 28 weeks after infection. The expression of ATG5 and Beclin-1 was examined by immunohistochemistry, and both were expressed in the glandular epithelial cells of the gastric mucosal tissue, and HP-infected mice were diffuse and higher than non-infected mice. These results indicate that HP infection causes severe dysplasia in INS-GAS mice, and that autophagy is strongly induced over time due to persistent infection.

Academic Significance and Societal Importance of the Research Achievements

オートファジーは細胞内分解機構の一つであり、細胞の恒常性の維持において主要な役割を果たしている。癌、感染症等様々な疾患や病態へ関与が報告され、癌細胞に対しては腫瘍抑制・促進の両方の作用を有していることが明らかにされ、治療応用への試みも行われてきている。今回の胃発癌マウスモデルを用いた検討では、オートファジーは炎症性胃発癌機序に関与している可能性が示された。さらなる検討により新たな治療法へのアプローチが期待される。