Oxidative stress effect on the activation of hepatic stellate cells

Collagen is the most excessive extracellular matrix protein in hepatic fibrosis. Activated, but not quiescent, hepatic stellate cells (HSCs) have a high level of collagen and a smooth muscle actin (alpha SMA) expression. HSCs play a key role in the pathogenesis of hepatic fibrosis. We analyzed a mechanism leading to HSC activation by evaluating the role of oxidative stress and the expression of NFkB. In vitro study HSCs were proliferated (PCNA:2% vs 68%) and activated (alpha SMA: 5% vs 78%) by ascorbate/FeSO4, and HSCs activated by type I collagen were blocked (PCNA: 97% vs 4%, a SMA: 86% vs 9%) by a-tocopherol. In vivo study means of a SMA positive cells in liver at 400 x HPF were 48.3+/-5.2 and 15.2+/-1.8 and [3H]thymidine uptake of HSC was 529.2+/-284.8 cpm and 223.0+/-86.3 cpm in control and a-tocopherol treated group respectively at 32 hours after CCl4 injection. Nuclear extracts from activated, but not from quiescent, HSCs formed a complex with the NFkB cognate oligonucleotidesand alpha-tocopherol inhibited this bindings. This study indicates that oxidative stress plays an essential role through the induction of NFkB on HSC activation.