RIP3 attenuates the pancreatic damage induced by deletion of ATG7

• Verfasst von: Zhou, Xiaodong [VerfasserIn]
• Verfasst von: Xie, Li [VerfasserIn]
• Verfasst von: Xia, Leizhou [VerfasserIn]
• Verfasst von: Zhou, Xiaodong [VerfasserIn]
• Verfasst von: Bergmann, Frank [VerfasserIn]
• Verfasst von: Büchler, Markus W. [VerfasserIn]
• Verfasst von: Hackert, Thilo [VerfasserIn]
• Verfasst von: Fortunato, Franco [VerfasserIn]
• Titel: RIP3 attenuates the pancreatic damage induced by deletion of ATG7
• Verf.angabe: Xiaodong Zhou, Li Xie, Leizhou Xia, Frank Bergmann, Markus W. Büchler, Guido Kroemer, Thilo Hackert and Franco Fortunato
• E-Jahr: 2017
• Jahr: 13 July 2017
• Umfang: 10 S.
• Fussnoten: Gesehen am 10.07.2020
• Titel Quelle: Enthalten in: Cell death & disease
• Ort Quelle: London [u.a.] : Nature Publishing Group, 2010
• Jahr Quelle: 2017
• Band/Heft Quelle: 8(2017,7) Artikel-Nummer e2918, 10 Seiten
• ISSN Quelle: 2041-4889
• DOI: doi:10.1038/cddis.2017.313
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 157846305X

Abstract

Invalidation of pancreatic autophagy entails pancreatic atrophy, endocrine and exocrine insufficiency and pancreatitis. The aim of this study was to investigate whether depletion of Rip3, which is involved in necroptotic signaling, may attenuate the pancreatic atrophy and pancreatitis resulting from autophagy inhibition. Autophagy and necroptosis signaling were evaluated in mice lacking expression of Rip3 in all organs and Atg7 in the pancreas. Acinar cell death, inflammation and fibrosis were evaluated by using of a compendium of immunofluorescence methods and immunoblots. Mice deficient for pancreatic Atg7 developed acute pancreatitis, which progressed to chronic pancreatitis. This phenotype reduces autophagy, increase apoptosis and necroptosis, inflammation and fibrosis, as well as premature death of the animals. Knockout of Rip3 exacerbated the apoptotic death of acinar cells, increased tissue damage, reduced macrophage infiltration and further accelerated the death of the mice with Atg7-deficient pancreas. The pancreatic degeneration induced by autophagy inhibition was exacerbated by Rip3 deletion.