Osteopontin expression in normal and fibrotic liver.: Altered liver healing in. osteopontin-deficient mice
Osteopontin expression in normal and fibrotic liver.: Altered liver healing in. osteopontin-deficient mice
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DOI：
10.1016/j.jhep.2005.07.024
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发表时间：
2006-02-01
影响因子：
25.7
通讯作者：
Desmoulière, A
中科院分区：
文献类型：
--
作者：
Lorena, D;Darby, IA;Desmoulière, A
背景/目的：骨桥蛋白与许多病理生理学事件有关。骨桥蛋白表达在正常和肝纤维化和肝纤维化在骨桥蛋白缺陷mice.Methods：肝纤维化诱导的小鼠和大鼠四氯化碳（CCl 4）治疗或胆管结扎。肝脏用于常规组织学、骨桥蛋白免疫组织化学和原位杂交或蛋白质和RNA提取。结果：在正常小鼠肝脏中，骨桥蛋白mRNA表达很低。CCl 4处理或胆管结扎后，骨桥蛋白mRNA表达增加。骨桥蛋白在正常肝和肝纤维化的胆管上皮细胞中均有表达。在CCl 4治疗开始后不久，骨桥蛋白也存在于坏死区域的炎性细胞中。在骨桥蛋白缺陷的小鼠，单剂量的CCl 4后，和慢性CCl 4治疗后的纤维化坏死面积显着增加相比，野生型治疗mice.Conclusions：我们的研究结果表明，骨桥蛋白的表达增加肝纤维化。此外，骨桥蛋白缺乏的小鼠对CCl 4治疗更敏感，在最初的步骤中显示出更多的坏死（可能是由于一氧化氮产生不足），此后出现更多的纤维化。在肝纤维化过程中观察到的骨桥蛋白表达的增加可能起保护作用。(C)2005年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background/Aims: Osteopontin has been implicated in numerous physiopathological events. Osteopontin expression in normal and fibrotic liver and liver fibrogenesis in osteopontin-deficient mice were studied.Methods: Fibrosis was induced in mice and rats by carbon tetrachloride (CCl4) treatment or bile duct ligation. The liver was used for conventional histology, osteopontin immunohistochemistry and in situ hybridization, or protein and RNA extraction. In mice, necrotic areas and fibrosis were evaluated by quantitative image analysis.Results: In normal liver, osteopontin mRNA expression was very low. After CCl4 treatment or bile duct ligation, osteopontin mRNA expression was increased. Osteopontin was expressed by biliary epithelial cells in normal and fibrotic liver. Soon after the beginning of the CCl4 treatment, osteopontin was also present in inflammatory cells of the necrotic areas. In osteopontin-deficient mice, necrotic areas after a single dose Of CCl4, and fibrosis after chronic CCl4 treatment were significantly increased as compared with wild-type treated mice.Conclusions: Our results show that osteopontin expression increases during liver fibrogenesis. Furthermore, osteopontin-deficient mice were more susceptible to CCl4 treatment, displaying more necrosis during the initial steps (probably due to a deficiency in nitric oxide production) and more fibrosis thereafter. The increase in osteopontin expression observed during liver fibrogenesis may play a protective role. (C) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.