Overexpression of thioredoxin prevents thioacetamide-induced hepatic fibrosis in mice
Overexpression of thioredoxin prevents thioacetamide-induced hepatic fibrosis in mice
复制标题
DOI：
10.1016/j.jhep.2004.09.020
复制
发表时间：
2005-01-01
影响因子：
25.7
通讯作者：
Yodoi, J
中科院分区：
文献类型：
--
作者：
Okuyama, H;Nakamura, H;Yodoi, J
背景/目的：硫氧还蛋白是一种具有抗氧化和抗凋亡作用的小型氧化还原活性蛋白。我们之前曾报道，硫氧还蛋白转基因小鼠中硫代乙酰胺诱导的急性肝炎得到减弱。本研究的目的是探讨硫氧还蛋白对肝纤维化的保护作用。方法：我们对硫氧还蛋白转基因小鼠进行硫代乙酰胺诱导的肝纤维化。我们还研究了硫氧还蛋白对原代培养的肝星状细胞活化过程的影响。结果：硫代乙酰胺诱导的小鼠和大鼠纤维化肝脏的肝细胞中诱导了内源性硫氧还蛋白的表达。硫氧还蛋白的过度表达抑制肿瘤坏死因子-α诱导的 HepG2 细胞凋亡。与野生型小鼠相比，转基因小鼠中硫代乙酰胺诱导的纤维化和丙二醛积累受到抑制。从转基因小鼠中分离的肝星状细胞的增殖能力低于从野生型小鼠中分离的肝星状细胞。重组硫氧还蛋白在血清或血小板源性生长因子刺激下显着抑制原代培养的星状细胞的DNA合成。结论：硫氧还蛋白具有通过抑制氧化应激和抑制星状细胞增殖来减轻肝纤维化的潜力。 (C) 2004 年由 Elsevier B.V. 代表欧洲肝脏研究协会出版。
Background/Aims: Thioredoxin is a small redox-active protein with anti-oxidant and anti-apoptotic effects. We have previously reported that thioacetamide-induced acute hepatitis was attenuated in thioredoxin transgenic mice. The aim of the present study was to investigate the protective effect of thioredoxin for hepatic fibrosis.Methods: We subjected thioredoxin transgenic mice to thioacetamide-induced hepatic fibrosis. We also studied the effect of thioredoxin on the activation process of primary-cultured hepatic stellate cell.Results: The expression of endogenous thioredoxin was induced in hepatocytes of thioacetamide-induced murine and rat fibrotic livers. Overexpression of thioredoxin inhibited tumor necrosis factor-alpha-induced apoptosis of HepG2 cells. T'hioacetamide-induced fibrosis and accumulation of malondialdehyde were suppressed in transgenic mice as compared with wild type mice. Hepatic stellate cells isolated from transgenic mice were less proliferative than those isolated from wild type mice. Recombinant thioredoxin significantly inhibited DNA synthesis of primary-cultured stellate cells under serum or platelet-derived growth factor stimulation.Conclusions: Thioredoxin has a potential to attenuate hepatic fibrosis via suppressing oxidative stress and inhibiting proliferation of stellate cells. (C) 2004 Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.