Genetic inactivation of Caspase 8 in hepatocytes ameliorates progression of MASH following Jnk deficiency
The study investigates the role of JNK1/JNK2 during MASH progression. In mice deficient for Jnk1 and Jnk2 in hepatocytes (Jnk1/2 delta hepa) subjected to two different MASH models, enhanced liver injury, fibrosis and oxidative stress were observed. RNA sequencing of liver tissue revealed up-regulated pathways in Jnk1/2 delta hepa livers (N=5), including inflammatory signals and apoptotic pathways compared to WT controls (N=5). Additional blocking of Caspase 8 signaling (JNK1/2 delta hepa Casp8 delta hepa; N=5) improved HFD-induced liver damage, fibrogenesis and oxidative stress.