The uncoordinated-5 homolog B receptor affects hepatic ischemia reperfusion injury

  • Recent evidence has demonstrated additional roles for the neuronal guidance protein receptor UNC5B outside the nervous system. Given the fact that ischemia reperfusion injury (IRI) of the liver is a common source of liver dysfunction and the role of UNC5B during an acute inflammatory response we investigated the role of UNC5B on acute hepatic IRI. We report here that UNC5B+/− mice display reduced hepatic IRI and neutrophil (PMN) infiltration compared to WT controls. This correlated with serum levels of lactate dehydrogenase (LDH), aspartate- (AST) and alanine- (ALT) aminotransferase, the presence of PMN within ischemic hepatic tissue, and serum levels of inflammatory cytokines. Moreover, injection of an anti-UNC5B antibody resulted in a significant reduction of hepatic IR injury. This was associated with reduced parameters of liver injury (LDH, ALT, AST) and accumulation of PMN within the injured hepatic tissue. In conclusion our studies demonstrate a significant role for UNC5B in the development of hepatic IRI and identified UNC5B as a potential drug target to prevent liver dysfunction in the future.

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Metadaten
Author:Klemens König, David Köhler, Tiago Granja, Carla JenneweinGND, Thi Hoai Nguyen TranGND, Valbona Mirakaj, Friedemann Kröhnert, Peter Rosenberger
URN:urn:nbn:de:hebis:30:3-257276
DOI:https://doi.org/10.1371/journal.pone.0041085
ISSN:1932-6203
Parent Title (English):PLoS One
Publisher:PLoS
Place of publication:Lawrence, Kan.
Document Type:Article
Language:English
Date of Publication (online):2012/07/25
Date of first Publication:2012/07/25
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2012/08/13
Volume:7
Issue:(7):e41085
Page Number:8
HeBIS-PPN:35791810X
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 3.0