Hepatic stellate cells (HSCs), that are normally quiescent, represent a major cell type responsible for liver fibrogenesis. Upon chronic liver injury, quiescent HSCs become activated and α-SMA is used as a marker for activated HSCs (32). Activated HSCs synthesize and secrete extra fibrillar collagen-I, which contributes to liver fibrosis (32). In primary isolated mouse HSCs, CYP2A5, but not CYP2E1, was detected by western blotting analysis (Supplementary Figure S1). Usually, the Lieber-Decarli ethanol model does not induce fibrosis. In fact, although we detected more collagen deposit after ethanol feeding, no fibrosis was observed. In another model of liver fibrosis, bile duct ligation (BDL)-induced liver fibrosis was more severe in cyp2a5−/− than cyp2a5+/+ mice (Supplementary Figure S2). Whether CYP2A5 in HSCs can be induced by ethanol feeding and whether CYP2A5 in HSCs may inhibit HSCs activation and protect against liver fibrogenesis require further studies.
