Combined activities of JNK1 and JNK2 in hepatocytes protect against toxin-induced liver injury

Manuscript Number: GASTRO-D-14-01639R2 Full Title: Combined activities of JNK1 and JNK2 in hepatocytes protect against toxin-induced liver injury Article Type: Basic Liver Section/Category: Basic Corresponding Author: Christian Trautwein, M.D. University Hospital, RWTH Aachen Aachen, GERMANY Corresponding Author Secondary Information: Corresponding Author's Institution: University Hospital, RWTH Aachen Corresponding Author's Secondary Institution: First Author: Francisco Javier Cubero First Author Secondary Information: Order of Authors: Francisco Javier Cubero Miguel Eugenio Zoubek Jin Peng Wei Hu Gang Zhao Yulia A. Nevzorova Malika Al Masaoudi Lars P. Bechmann Mark V. Boekschoten Michael Muller Nikolaus Gassler Christian Preisinger Ali E. Canbay Tom Luedde Roger J Davis Christian Liedtke Christian Trautwein, M.D. Order of Authors Secondary Information: Abstract: Background&Aims: c-Jun N-terminal kinase (JNK)1 and JNK2 are expressed in hepatocytes and have overlapping and distinct functions. JNK proteins are activated, via phosphorylation, in response to acetaminophenor CCl4-induced liver damage; the level of activation correlates with the degree of injury. SP600125, a JNK inhibitor, has been reported to block acetaminophen-induced liver injury. We investigated the role of JNK in drug-induced liver injury (DILI) in liver tissues from patients and in mice with genetic deletion of JNK in hepatocytes. Methods: We studied liver sections from