The role of rab7 on ectopic activation of trypsin and the mechanism of the onset of acute pancreatitis.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08476
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Jichi Medical University
• Principal Investigator: MASHIMA Hirosato 自治医科大学, 医学部, 教授 (10261869)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 急性膵炎 / Rab7 / トリプシン / 酵素顆粒 / リソソーム

Outline of Final Research Achievements

Through the analysis of Rab7 KO mice, we have shown 1. Rab7 plays an important role in the maturation and integrity of zymogen granule and lysosome, 2. Zymogen granule and lysosome are altered in integrity in Rab7 KO acinar cells and the activity of cathepsin B is already elevated in a physiological condition, 3. Excessive stimulation of secretion to the immature zymogen granules together with fragile lysosomes results in the abnormal ectopic activation of trypsin in Rab7 KO acinar cells, 4. The number of Rab7-positieve cells (other than acinar cells) increased in the very early phase of experimental pancreatitis in Rab7-KO pancreas. Further investigation is needed on the types of Rab7-positive cells and whether they have a suppressive effect on pancreatitis.

Free Research Field

膵臓

Academic Significance and Societal Importance of the Research Achievements

Rab7が膵腺房細胞の恒常性の維持に重要な役割を果たしていること、膵炎に対して抑制的に作用することが明らかとなった。Rab7 KOマウスの実験的膵炎のごく初期に見られたRab7陽性細胞の正体、その果たしている役割を詳細に解析することで、膵炎の新たな治療法の開発につながる可能性がある。