プレゼンテーション情報

【論文】秋田大学(現労働者健康安全機構)の大西先生との共同研究成果がScientific Reportsに採択されました。 (更新 2017.08.02)
秋田大学(現労働者健康安全機構)の大西先生との共同研究「急性膵炎のモデルマウス」です。
和田先生が作成したrab7 KOで膵炎モデルができるという話になります。

Sci Rep. 2017 Jun 6;7(1):2817. doi: 10.1038/s41598-017-02988-3.

Disruption of Small GTPase Rab7 Exacerbates the Severity of Acute Pancreatitis in Experimental Mouse Models.

Takahashi K1, Mashima H2, Miura K1, Maeda D3, Goto A3, Goto T1, Sun-Wada GH4, Wada Y5, Ohnishi H6,7.

1 Department of Gastroenterology and Hepato-Biliary-Pancreatology, Akita University Graduate School of Medicine, Akita, Japan.
2 Department of Gastroenterology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
3 Department of Cellular and Organ Pathology, Akita University Graduate School of Medicine, Akita, Japan.
4 Department of Biochemistry, Faculty of Pharmaceutical Sciences, Doshisha Women's College, Kyoto, Japan.
5 Division of Biological Science, Institute of Scientific and Industrial Research, Osaka University, Osaka, Japan.
6 Department of Gastroenterology, Saitama Medical Center, Jichi Medical University, Saitama, Japan. hirohide-ohnishi@honbu.johas.go.jp.
7 Japan Organization of Occupational Health and Safety, Kanagawa, Japan. hirohide-ohnishi@honbu.johas.go.jp.

Abstract

Although aberrations of intracellular vesicle transport systems towards lysosomes including autophagy and endocytosis are involved in the onset and progression of acute pancreatitis, the molecular mechanisms underlying such aberrations remain unclear. The pathways of autophagy and endocytosis are closely related, and Rab7 plays crucial roles in both. In this study, we analyzed the function of Rab7 in acute pancreatitis using pancreas-specific Rab7 knockout (Rab7Δpan) mice. In Rab7Δpan pancreatic acinar cells, the maturation steps of both endosomes and autophagosomes were deteriorated, and the lysosomal functions were affected. In experimental models of acute pancreatitis, the histopathological severity, serum amylase concentration and intra-pancreatic trypsin activity were significantly higher in Rab7Δpan mice than in wild-type mice. Furthermore, the autophagy process was blocked in Rab7Δpan pancreas compared with wild-type mice. In addition, larger autophagic vacuoles that colocalize with early endosome antigen 1 (EEA1) but not with lysosomal-associated membrane protein (LAMP)-1 were much more frequently formed in Rab7Δpan pancreatic acinar cells. Accordingly, Rab7 deficiency exacerbates the severity of acute pancreatitis by impairing the autophagic and endocytic pathways toward lysosomes.