title: The uncoordinated-5 homolog B receptor affects hepatic ischemia reperfusion injury.
abstract: 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.
authors: Department of Anaesthesiology and Intensive Care Medicine, Tübingen University Hospital, Eberhard-Karls University Tübingen, Tübingen, Germany.
authors: Klemens
authors: K
authors: König
authors: David
authors: D
authors: Köhler
authors: Tiago
authors: T
authors: Granja
authors: Carla
authors: C
authors: Jennewein
authors: Nguyen
authors: N
authors: Tran
authors: Valbona
authors: V
authors: Mirakaj
authors: Friedemann
authors: F
authors: Kröhnert
authors: Peter
authors: P
authors: Rosenberger
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D000075386:Netrin Receptors; D020556:Neutrophil Infiltration / Q000235:genetics; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
chemical_list: D000075386:Netrin Receptors; D011956:Receptors, Cell Surface; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase