Inflammatory and cell-death-related pathways in liver fibrosis: Cell-type specific approaches to novel therapies ((1)-P06)

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The kinase RIPK3 regulates a novel form of programmed cell death called 'necroptosis' and other signaling pathways involved in cell death and inflammation. In the 2nd funding period, we could demonstrate that RIPK3 is overexpressed in human non-alcoholic steatohepatitis (NASH) and mediates NASH fibrosis in mice. In the 3rd funding period, P06 will therefore further elaborate the molecular targets of RIPK3 in NASH fibrosis and will put a major focus on translational aspects. Moreover, the project will investigate the important question if induction of programmed cell death in HSC via apoptosis (Caspase-dependent) or necroptosis (RIPK3-dependent) can prevent fibrosis.