ABSTRACT: Non-alcoholic steatohepatitis (NASH), has emerged as a major cause of liver failure and hepatocellular carcinoma. Although decades of studies have improved our understanding of its pathophysiology, the molecular mechanisms are still incompletely understood. In the current study, using a diet-induced mouse model of NASH, we performed RNA Sequencing analysis to reveal molecular features of NASH progression. As a result, we obtained hepatic genome-wide mRNA expression in the livers from two groups of mice (NASH versus Normal).Using FDR < 0.01 and fold change > 2 as the threshold, we identified 1745 differentially expressed genes (DEGs) in the livers of NASH mice relative to the normal control mice, of which 1484 up-regulated and 261 down-regulated. The top 5 up-regulated genes included the genes encoding for Trem2, Lcn2, Ephb2, Mmp12 and Sprr1a.Gene ontology (GO) analysis showed that the up-regulated genes in NASH mice were mainly enriched in biological processes such as response to biotic stimulus, regulation of immune system process and myeloid leukocyte activation, while down-regulated genes were related to organonitrogen compound biosynthetic process and organic acid metabolic process.KEGG pathway enrichment results showed that up-regulated genes were mainly enriched in toll like receptor signaling, regulation of actin cytoskeleton, leukocyte transendothelial migration, chemokine signal pathway as well as cytokine and cytokine receptor interaction, while down-regulated gene clusters were mainly enriched in and steroid biosynthetic as well as glycine serine and threonine metabolism.Meanwhile, as expected, genes involved in hepatic lipogenesis (Srebp-1c, Fasn and Scd-1), lipid absorption (CD36), inflammation (Tnfa, IL1b and Ccl2), and fibrosis (Col1a1, Tgfb1 and Mmp13), are up-regulated in NASH mice.Our study may help to uncover NASH molecular basis and provide therapeutic targets for its treatment.
