Identification of molecular signals essential for intestinal epithelialization of gastric gland ducts.

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15917
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Tsuboi Mayo 東京大学, 医学部附属病院, 助教 (40895421)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 胃癌 / 胃炎 / 腸上皮化生 / 免疫応答

Outline of Final Research Achievements

The characteristics and developmental mechanisms of intestinal metaplasia in the corpus were examined using a mouse model of intestinal metaplasia.RNA sequencing and CyTOF/FACS showed that no immune response is involved in intestinal　metaplasia, and similar results were obtained in the mouse model. Since previous studies have shown that activation of the Ras/MAPK pathway is required, we crossed T1-Cdx2 mice with mice in which parietal cells were selectively ablated and further induced intestinal epithelialization by inhabiting notch signal.
The results of this study indicate that both Kras activation and Notch inhibition may be required for the development of intestinal transformation in the gastric body. These findings provide insight into the mechanisms of gastric cancer and intestinal metaplasia.

Free Research Field

発癌

Academic Significance and Societal Importance of the Research Achievements

腸上皮化生は発がんの過程で、胃に生じる変化であるが、その意義や発生機序は明らかでない。多数ある胃炎マウスモデルを多角的に解析することで、腸上皮化生の発生、進展においては胃炎における獲得免疫応答は重要な要素ではないことを示した。
ヒトの腸上皮化生を呈する既報の胃炎モデルはないなかで、新規腸上皮化生マウスモデルを樹立した。さらに、胃体部の腸上皮化生発生機序にRas/MAPK経路活性化が重要な役割をもつことを示した。
胃炎・胃癌の発生メカニズムには未知の点が多い中で、ヒト胃炎～腸上皮化生～胃癌発生に至る多段階発がんの病態理解、新規治療開発に貢献しうる成果を示した。