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

激酶RIPK3调节一种新形式的程序性细胞死亡，称为“坏死性凋亡”和其他参与细胞死亡和炎症的信号通路。在第二个资助期，我们可以证明RIPK3在人类非酒精性脂肪性肝炎（NASH）中过表达，并介导小鼠的NASH纤维化。因此，在第三个资助期，P06将进一步阐述RIPK3在NASH纤维化中的分子靶点，并将主要关注翻译方面。此外，该项目将研究通过凋亡（Caspase依赖性）或坏死性凋亡（RIPK3依赖性）诱导HSC中的程序性细胞死亡是否可以预防纤维化的重要问题。

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.