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.
Lee
K S
KS
Department of Internal Medicine, Yonsei Universit, College of Medicine, Seoul, Korea. leeks519@yumc.yonsei.ac.kr
Lee
S J
SJ
Park
H J
HJ
Chung
J P
JP
Han
K H
KH
Chon
C Y
CY
Lee
S I
SI
Moon
Y M
YM
D000199:Actins / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D008099:Liver / Q000166:cytology*; D008103:Liver Cirrhosis / Q000209:etiology* / Q000517:prevention & control; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D014810:Vitamin E / Q000494:pharmacology
D000199:Actins; D016326:Extracellular Matrix Proteins; D016328:NF-kappa B; D014810:Vitamin E