Intrahepatic lipocalin 2 promotes liver fibrosis in alcoholic hepatitis [array]

Our project is to explore the molecular subtypes for targeted therapies in Alcoholic Hepatitis (AH). We have found that LCN2 gene expression is markedly induced in AH patients and correlated to the disease severity including portal hypertension. Animal data from microarray experiments show that compared with the wild mice, LCN2 knockout mice are protected from CCl4-induced liver fibrosis. The focus of our current study is to investigate the effect of overexpression of LCN2 on functional changes in hepatocytes. To this end, HepG2 cells and human primary hepatocytes (HPH) were overexpressed human LCN2 gene and samples were analyzed through RNA-sequencing. To dissect the molecular mechanisms that mediate LCN2 fibrogenic effects in the injured liver, we performed transcriptome profiling analysis of Lcn2–/– and WT mice treated with CCl4. Liver tissue was collected from BALB/c WT and Lcn2-/- mice treated with CCl4 or corn oil for 4 weeks.