Increased hepatic fibrosis and JNK2-dependent liver injury in mice exhibiting hepatocyte-specific deletion of cFLIP

American Journal of Physiology - Gastrointestinal and Liver Physiology

Volumn 303, Issue 4, 2012, Pages

  Schattenberg, Jörn M ^a   Nagel, Michael ^a   Kim, Yong Ook ^a   Kohl, Tobias ^a   Wörns, Marcus A ^a   Zimmermann, Tim ^a   Schad, Arno ^a   Longerich, Thomas ^b   Schuppan, Detlef ^a   He, You Wen ^c   Galle, Peter R ^a   Schuchmann, Marcus ^a  

^a UNIVERSITY MEDICAL CENTER MAINZ   (Germany)

^b UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

^c DUKE UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

Apoptosis; Cellular FLICE inhibitory protein; cJun NH 2 terminal kinase 2

Indexed keywords

CARBON TETRACHLORIDE; CASPASE 3; CASPASE 8; FLICE INHIBITORY PROTEIN; JANUS KINASE 2; THIOACETAMIDE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DISEASE COURSE; ENZYME ACTIVATION; ENZYME PHOSPHORYLATION; GENE DELETION; IMMUNOHISTOCHEMISTRY; LIVER CELL; LIVER FIBROSIS; LIVER INJURY; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL;

ANIMALS; APOPTOSIS; CARBON TETRACHLORIDE; CASP8 AND FADD-LIKE APOPTOSIS REGULATING PROTEIN; CASPASE 3; CASPASE 9; DISEASE MODELS, ANIMAL; DISEASE PROGRESSION; DRUG-INDUCED LIVER INJURY; ENZYME ACTIVATION; EXTRACELLULAR SIGNAL-REGULATED MAP KINASES; GENOTYPE; HEPATOCYTES; LIVER; LIVER CIRRHOSIS; MALE; MICE; MICE, KNOCKOUT; MITOGEN-ACTIVATED PROTEIN KINASE 9; PHENOTYPE; PHOSPHORYLATION; SIGNAL TRANSDUCTION; THIOACETAMIDE; TIME FACTORS;

EID: 84865240298     PISSN: 01931857     EISSN: 15221547     Source Type: Journal    
DOI: 10.1152/ajpgi.00525.2011     Document Type: Article

References (25)

1. Bataller R, Rombouts K, Altamirano J, Marra F. Fibrosis in alcoholic and nonalcoholic steatohepatitis. Best Pract Res Clin Gastroenterol 25: 231-244, 2011.
2. Ben Moshe T, Barash H, Kang TB, Kim JC, Kovalenko A, Gross E, Schuchmann M, Abramovitch R, Galun E, Wallach D. Role of caspase-8 in hepatocyte response to infection and injury in mice. Hepatology 45: 1014-1024, 2007.
3. Beraza N, Malato Y, Vander BS, Liedtke C, Wasmuth HE, Dreano M, de Vos R, Roskams T, Trautwein C. Pharmacological IKK2 inhibition blocks liver steatosis and initiation of non-alcoholic steatohepatitis. Gut 57: 655-663, 2008.
4. Berres ML, Koenen RR, Rueland A, Zaldivar MM, Heinrichs D, Sahin H, Schmitz P, Streetz KL, Berg T, Gassler N, Weiskirchen R, Proudfoot A, Weber C, Trautwein C, Wasmuth HE. Antagonism of the chemokine Ccl5 ameliorates experimental liver fibrosis in mice. J Clin Invest 120: 4129-4140, 2010.
5. Canbay A, Friedman S, Gores GJ. Apoptosis: the nexus of liver injury and fibrosis. Hepatology 39: 273-278, 2004.
6. Chang L, Kamata H, Solinas G, Luo JL, Maeda S, Venuprasad K, Liu YC, Karin M. The E3 ubiquitin ligase itch couples JNK activation to TNFalpha-induced cell death by inducing c-FLIP(L) turnover. Cell 124: 601-613, 2006.
7. Chang TT, Liaw YF, Wu SS, Schiff E, Han KH, Lai CL, Safadi R, Lee SS, Halota W, Goodman Z, Chi YC, Zhang H, Hindes R, Iloeje U, Beebe S, Kreter B. Longterm entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B. Hepatology 52: 886-893, 2010.
8. Choi SS, Omenetti A, Witek RP, Moylan CA, Syn WK, Jung Y, Yang L, Sudan DL, Sicklick JK, Michelotti GA, Rojkind M, Diehl AM. Hedgehog pathway activation and epithelial-to-mesenchymal transitions during myofibroblastic transformation of rat hepatic cells in culture and cirrhosis. Am J Physiol Gastrointest Liver Physiol 297: G1093-G1106, 2009.
9. Hernandez-Gea V, Friedman SL. Pathogenesis of liver fibrosis. Annu Rev Pathol 6: 425-456, 2011.
10. Hikita H, Takehara T, Kodama T, Shimizu S, Shigekawa M, Hosui A, Miyagi T, Tatsumi T, Ishida H, Li W, Kanto T, Hiramatsu N, Shimizu S, Tsujimoto Y, Hayashi N. Delayed-onset caspase-dependent massive hepatocyte apoptosis upon Fas activation in Bak/Bax-deficient mice. Hepatology 54: 240-251, 2011.
11. Jiao J, Sastre D, Fiel MI, Lee UE, Ghiassi-Nejad Z, Ginhoux F, Vivier E, Friedman SL, Merad M, Aloman C. Dendritic cell regulation of carbon tetrachloride-induced murine liver fibrosis regression. Hepatology 55: 244-255, 2012.
12. Joka D, Wahl K, Moeller S, Schlue J, Vaske B, Bahr MJ, Manns MP, Schulze-Osthoff K, Bantel H. Prospective biopsy-controlled evaluation of cell death biomarkers for prediction of liver fibrosis and nonalcoholic steatohepatitis. Hepatology 55: 455-464, 2012.
13. Jung Y, Diehl AM. Non-alcoholic steatohepatitis pathogenesis: role of repair in regulating the disease progression. Dig Dis 28: 225-228, 2010.
14. Jung Y, Witek RP, Syn WK, Choi SS, Omenetti A, Premont R, Guy CD, Diehl AM. Signals from dying hepatocytes trigger growth of liver progenitors. Gut 59: 655-665, 2010.
15. Lee UE, Friedman SL. Mechanisms of hepatic fibrogenesis. Best Pract Res Clin Gastroenterol 25: 195-206, 2011.
16. Liedtke C, Bangen JM, Freimuth J, Beraza N, Lambertz D, Cubero FJ, Hatting M, Karlmark KR, Streetz KL, Krombach GA, Tacke F, Gassler N, Riethmacher D, Trautwein C. Loss of caspase-8 protects mice against inflammation-related hepatocarcinogenesis but induces non-apoptotic liver injury. Gastroenterology 141: 2176-2187, 2011.
17. Popov Y, Sverdlov DY, Bhaskar KR, Sharma AK, Millonig G, Patsen-ker E, Krahenbuhl S, Krahenbuhl L, Schuppan D. Macrophage-mediated phagocytosis of apoptotic cholangiocytes contributes to reversal of experimental biliary fibrosis. Am J Physiol Gastrointest Liver Physiol 298: G323-G334, 2010.
18. Poynard T, McHutchison J, Manns M, Trepo C, Lindsay K, Goodman Z, Ling MH, Albrecht J. Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C. Gastroenterology 122: 1303-1313, 2002.
19. Schattenberg JM, Singh R, Wang Y, Lefkowitch JH, Rigoli RM, Scherer PE, Czaja MJ. JNK1 but not JNK2 promotes the development of steatohepatitis in mice. Hepatology 43: 163-172, 2006.
20. Schattenberg JM, Worns MA, Zimmermann T, He YW, Galle PR, Schuchmann M. The role of death effector domain-containing proteins in acute oxidative cell injury in hepatocytes. Free Radic Biol Med 52: 1911-1917, 2012.
21. Schattenberg JM, Zimmermann T, Worns M, Sprinzl MF, Kreft A, Kohl T, Nagel M, Siebler J, Bergkamen HS, He YW, Galle PR, Schuchmann M. Ablation of c-FLIP in hepatocytes enhances death-receptor mediated apoptosis and toxic liver injury in vivo. J Hepatol 55: 1272-1280, 2011.
22. Schuppan D, Afdhal NH. Liver cirrhosis. Lancet 371: 838-851, 2008.
23. Wang Y, Schattenberg JM, Rigoli RM, Storz P, Czaja MJ. Hepatocyte resistance to oxidative stress is dependent on protein kinase C-mediated down-regulation of c-Jun/AP-1. J Biol Chem 279: 31089-31097, 2004.
24. Wang Y, Singh R, Lefkowitch JH, Rigoli RM, Czaja MJ. Tumor necrosis factor-induced toxic liver injury results from JNK2-dependent activation of caspase-8 and the mitochondrial death pathway. J Biol Chem 281: 15258-15267, 2006.
25. Weber LW, Boll M, Stampfl A. Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. Crit Rev Toxicol 33: 105-136, 2003.