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A20 prevents chronic liver inflammation and cancer by protecting hepatocytes from death

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Abstract
An important regulator of inflammatory signalling is the ubiquitin-editing protein A20 that acts as a break on nuclear factor-kappa B (NF-kappa B) activation, but also exerts important cytoprotective functions. A20 knockout mice are cachectic and die prematurely due to excessive multi-organ inflammation. To establish the importance of A20 in liver homeostasis and pathology, we developed a novel mouse line lacking A20 specifically in liver parenchymal cells. These mice spontaneously develop chronic liver inflammation but no fibrosis or hepatocellular carcinomas, illustrating an important role for A20 in normal liver tissue homeostasis. Hepatocyte-specific A20 knockout mice show sustained NF-kappa B-dependent gene expression in the liver upon tumor necrosis factor (TNF) or lipopolysaccharide injection, as well as hepatocyte apoptosis and lethality upon challenge with sublethal doses of TNF, demonstrating an essential role for A20 in the protection of mice against acute liver failure. Finally, chronic liver inflammation and enhanced hepatocyte apoptosis in hepatocyte-specific A20 knockout mice was associated with increased susceptibility to chemically or high fat-diet-induced hepatocellular carcinoma development. Together, these studies establish A20 as a crucial hepatoprotective factor.
Keywords
TRAIL-INDUCED APOPTOSIS, HEPATOCELLULAR-CARCINOMA, SIGNALING COMPLEXES, NF-KAPPA-B, CELL-PROLIFERATION, MEDIATED APOPTOSIS, JNK ACTIVATION, ENZYME A20, MICE, EXPRESSION

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Chicago
Catrysse, Leen, Morvarid Farhang Ghahremani, Lars Vereecke, SA Youssef, Conor Mc Guire, Mozes Sze, A Weber, et al. 2016. “A20 Prevents Chronic Liver Inflammation and Cancer by Protecting Hepatocytes from Death.” Cell Death & Disease 7.
APA
Catrysse, L., Farhang Ghahremani, M., Vereecke, L., Youssef, S., Mc Guire, C., Sze, M., Weber, A., et al. (2016). A20 prevents chronic liver inflammation and cancer by protecting hepatocytes from death. CELL DEATH & DISEASE, 7.
Vancouver
1.
Catrysse L, Farhang Ghahremani M, Vereecke L, Youssef S, Mc Guire C, Sze M, et al. A20 prevents chronic liver inflammation and cancer by protecting hepatocytes from death. CELL DEATH & DISEASE. 2016;7.
MLA
Catrysse, Leen, Morvarid Farhang Ghahremani, Lars Vereecke, et al. “A20 Prevents Chronic Liver Inflammation and Cancer by Protecting Hepatocytes from Death.” CELL DEATH & DISEASE 7 (2016): n. pag. Print.
@article{8023196,
  abstract     = {An important regulator of inflammatory signalling is the ubiquitin-editing protein A20 that acts as a break on nuclear factor-kappa B (NF-kappa B) activation, but also exerts important cytoprotective functions. A20 knockout mice are cachectic and die prematurely due to excessive multi-organ inflammation. To establish the importance of A20 in liver homeostasis and pathology, we developed a novel mouse line lacking A20 specifically in liver parenchymal cells. These mice spontaneously develop chronic liver inflammation but no fibrosis or hepatocellular carcinomas, illustrating an important role for A20 in normal liver tissue homeostasis. Hepatocyte-specific A20 knockout mice show sustained NF-kappa B-dependent gene expression in the liver upon tumor necrosis factor (TNF) or lipopolysaccharide injection, as well as hepatocyte apoptosis and lethality upon challenge with sublethal doses of TNF, demonstrating an essential role for A20 in the protection of mice against acute liver failure. Finally, chronic liver inflammation and enhanced hepatocyte apoptosis in hepatocyte-specific A20 knockout mice was associated with increased susceptibility to chemically or high fat-diet-induced hepatocellular carcinoma development. Together, these studies establish A20 as a crucial hepatoprotective factor.},
  articleno    = {e2250},
  author       = {Catrysse, Leen and Farhang Ghahremani, Morvarid and Vereecke, Lars and Youssef, SA and Mc Guire, Conor and Sze, Mozes and Weber, A and Heikenwalder, M and de Bruin, A and Beyaert, Rudi and van Loo, Geert},
  issn         = {2041-4889},
  journal      = {CELL DEATH \& DISEASE},
  language     = {eng},
  pages        = {10},
  title        = {A20 prevents chronic liver inflammation and cancer by protecting hepatocytes from death},
  url          = {http://dx.doi.org/10.1038/cddis.2016.154},
  volume       = {7},
  year         = {2016},
}

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