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

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 endocytos...

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Autores principales:	Kenichi Takahashi, Hirosato Mashima, Kouichi Miura, Daichi Maeda, Akiteru Goto, Takashi Goto, Ge-Hong Sun-Wada, Yoh Wada, Hirohide Ohnishi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/01e478d6315949b28c0e5adb4f4589ec
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spelling	oai:doaj.org-article:01e478d6315949b28c0e5adb4f4589ec2021-12-02T16:06:06ZDisruption of Small GTPase Rab7 Exacerbates the Severity of Acute Pancreatitis in Experimental Mouse Models10.1038/s41598-017-02988-32045-2322https://doaj.org/article/01e478d6315949b28c0e5adb4f4589ec2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02988-3https://doaj.org/toc/2045-2322Abstract 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.Kenichi TakahashiHirosato MashimaKouichi MiuraDaichi MaedaAkiteru GotoTakashi GotoGe-Hong Sun-WadaYoh WadaHirohide OhnishiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kenichi Takahashi Hirosato Mashima Kouichi Miura Daichi Maeda Akiteru Goto Takashi Goto Ge-Hong Sun-Wada Yoh Wada Hirohide Ohnishi Disruption of Small GTPase Rab7 Exacerbates the Severity of Acute Pancreatitis in Experimental Mouse Models
description	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.
format	article
author	Kenichi Takahashi Hirosato Mashima Kouichi Miura Daichi Maeda Akiteru Goto Takashi Goto Ge-Hong Sun-Wada Yoh Wada Hirohide Ohnishi
author_facet	Kenichi Takahashi Hirosato Mashima Kouichi Miura Daichi Maeda Akiteru Goto Takashi Goto Ge-Hong Sun-Wada Yoh Wada Hirohide Ohnishi
author_sort	Kenichi Takahashi
title	Disruption of Small GTPase Rab7 Exacerbates the Severity of Acute Pancreatitis in Experimental Mouse Models
title_short	Disruption of Small GTPase Rab7 Exacerbates the Severity of Acute Pancreatitis in Experimental Mouse Models
title_full	Disruption of Small GTPase Rab7 Exacerbates the Severity of Acute Pancreatitis in Experimental Mouse Models
title_fullStr	Disruption of Small GTPase Rab7 Exacerbates the Severity of Acute Pancreatitis in Experimental Mouse Models
title_full_unstemmed	Disruption of Small GTPase Rab7 Exacerbates the Severity of Acute Pancreatitis in Experimental Mouse Models
title_sort	disruption of small gtpase rab7 exacerbates the severity of acute pancreatitis in experimental mouse models
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/01e478d6315949b28c0e5adb4f4589ec
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Disruption of Small GTPase Rab7 Exacerbates the Severity of Acute Pancreatitis in Experimental Mouse Models

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