RNA-Seq Reveals Enhanced Inflammation and Fibrosis in Alcohol-Induced Liver Injury of Apoe Knockout Mice

Alcohol-related liver disease (ALD) involves inflammation, hepatocellular damage, and fibrosis. Apolipoprotein E (Apoe) plays a role in immune regulation and tissue repair, but its function in ALD remains unclear. To explore this, we performed RNA sequencing on liver tissues from wild-type (WT) and Apoe knockout (Apoe KO) mice subjected to a chronic-plus-binge ethanol model. Gene expression analysis revealed distinct clustering between groups and significant alterations in pathways related to neutrophil degranulation, extracellular matrix organization, and collagen formation, indicating heightened inflammation and fibrosis in Apoe KO mice. These findings offer insights into Apoe’s role in ALD and liver repair. Mice subjected to the chronic-plus-binge ethanol-feeding model were fed as described in our previous study. Briefly, 10–12-week-old female mice were acclimated by ad libitum feeding with the Lieber-DeCarli liquid diet (catalog #F1259SP, Bio-Serv) for five days. Following acclimatization, the ethanol-fed groups received a Lieber-DeCarli ethanol diet (catalog #F1258SP, Bio-Serv) containing 5% (v/v) ethanol for 10 days. On day 11, a single dose of ethanol (5 g/kg body weight) was administered via oral gavage in the early morning, and the mice were euthanized nine hours later. Pair-fed control mice were maintained on an isocaloric control diet for 10 days and, on the day of euthanasia, received an oral gavage of isocaloric dextrin-maltose (9 g/kg body weight).