Yonsei Med J.  2001 Feb;42(1):1-8. 10.3349/ymj.2001.42.1.1.

Oxidative stress effect on the activation of hepatic stellate cells

• Lee KS
• Lee SJ
• Park HJ
• Chung JP
• Han KH
• Chon CY
• Lee SI
• Moon YM

• KMID: 720581
• DOI: http://doi.org/10.3349/ymj.2001.42.1.1

Abstract

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.

Keyword

Hepatic stellate cell; oxidative stress; NFkB

MeSH Terms

Actins/metabolism
Animal
Cells, Cultured
Extracellular Matrix Proteins/metabolism
Liver/cytology*
Liver Cirrhosis/prevention & control
Liver Cirrhosis/etiology*
Male
NF-kappa B/metabolism*
Oxidative Stress*
Rats
Rats, Sprague-Dawley
Vitamin E/pharmacology