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Systems Biology of Cell Death in Hepatocytes

Abstract:

The processes of liver regeneration and liver disease are regulated by a complex network of soluble and cell-associated apoptotic and inflammatory signals. To obtain insights into the mechanistic interplay of these signals and to define new therapeutic strategies, the combination of experimental data and mathematical modeling is a promising systems biological approach. Here, we review recent results in death receptor-mediated hepatocyte apoptosis focusing on Fas/CD95 and TNFa-mediated cell death. In this context, we present two complementary approaches of modeling death receptor-mediated cell death in hepatocytes. On the one hand we describe an ODE model of TNFa and FasL sensitising, which was extended by adding the regulation of pJNK and the generation of ROS after combined TNFa and ActD treatment and in which a published NF-kB model was integrated. This model is suitable for the integration of further pathway models, thus contributing to a better understanding of the network. On the other hand a literature-based and in parts experimentally validated comprehensive Boolean model of the central intrinsic and extrinsic apoptosis pathways as well as pathways connected with them is described. In the future, the according mathematical models will be a valuable approach to understand the complex crosstalks and interactions within hepatocytes and between different cells in the liver. Thus,
modeling of apoptosis in hepatocytes will proceed on different routes on the way to a functional representation of the whole liver.

10.1007/978-1-4614-4009-3_5

Projects: A2.2: Regulation of pro-apoptotic and anti-apoptotic responses in hepato..., Showcase LPS and Inflammation

Systems Biology of Apoptosis
Systems Biology of Apoptosis : 101
2013

Rebekka Schlatter, Kathrin Schmich, Christoph Borner, Michael Ederer, Irmgard Merfort

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[Christoph Borner] [Michael Ederer] [Irmgard Merfort]

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Views: 1925
  • Created: 7th Oct 2012 at 15:22
  • Last updated: 23rd Jul 2015 at 13:38

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