2022 Fiscal Year Final Research Report
Spatiotemporal analysis of gastric metaplasia and development of gastric mucosa regenerative therapy
| Project/Area Number |
20K08377
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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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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 化生 / 胃癌 / 炎症 / 相互作用 |
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| Outline of Final Research Achievements |
In this study, we generated novel mouse strains using stomach specific IL-33 expression or SOX9 deletion, in which gastric metaplasia developed corpus or antrum specific manners. Metaplasia can be rapidly induced by exogeneous treatment with tamoxifen in former strain, enabling us to investigate the acute phase of metaplasia. TFF1cre;IL33 mouse showed chronic metaplasia. In addition, SOX9 KO model developed chronic metaplasia with antrum dominant gastritis. All models showed dense CD45+ inflammatory cell infiltration around the metaplastic epithelium, indicating the critical role of inflammatory cells in metaplasia development. In these models, characteristics of metaplastic epithelium were different between corpus and antrum metaplasia, suggesting location specific metaplastic process. RNA from metaplastic epithelium showed enhanced chemokine and adhesion molecule expression, which may be the mediator of interactions between epithelium and inflammatory cells in metaplasia development.
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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 |
胃粘膜の化生はピロリ菌感染などにともなって発生する前癌病変として知られているが、その発生機序は明らかになっておらず、化生粘膜の再生、治療法は確立されていない。本課題において新規の化生発生モデルが樹立され、発生機序の解明や治療法の開発に役立つと考える。とくに動物モデルを用いることで初めて明らかになった炎症細胞との相互作用については、キーメディエーターであるケモカインをブロックすること、もしくは炎症細胞そのものを標的として枯渇させることなどによって化生粘膜の再生、もしくは再分化を可能とする新規治療となる可能性がある。また化生粘膜からの発癌機序、発癌の予防法についても研究が展開可能となった。
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