Lorena Dionne, Darby Ian A, Gadeau Alain-Pierre, Leen Laetitia Lam Shang, Rittling Susan, Porto Luís C, Rosenbaum Jean, Desmoulière Alexis
Groupe de Recherches pour l'Etude du Foie, Inserm E0362, Institut Fédératif de Recherche 66, Pathologies Infectieuses et Cancers, Université Victor Segalen Bordeaux 2, Bordeaux, France.
J Hepatol. 2006 Feb;44(2):383-90. doi: 10.1016/j.jhep.2005.07.024. Epub 2005 Aug 15.
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.
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.
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.
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.
背景/目的：骨桥蛋白与众多生理病理事件相关。本研究对正常肝脏和纤维化肝脏中骨桥蛋白的表达以及骨桥蛋白缺陷小鼠的肝纤维化形成情况进行了研究。
通过四氯化碳（CCl4）处理或胆管结扎诱导小鼠和大鼠发生纤维化。取肝脏用于常规组织学检查、骨桥蛋白免疫组织化学和原位杂交，或蛋白质与RNA提取。在小鼠中，通过定量图像分析评估坏死区域和纤维化情况。
在正常肝脏中，骨桥蛋白mRNA表达非常低。经CCl4处理或胆管结扎后，骨桥蛋白mRNA表达增加。在正常和纤维化肝脏中，胆管上皮细胞表达骨桥蛋白。CCl4处理开始后不久，坏死区域的炎性细胞中也出现骨桥蛋白。与野生型处理小鼠相比，在骨桥蛋白缺陷小鼠中，单次给予CCl4后的坏死区域以及慢性CCl4处理后的纤维化程度均显著增加。
我们的结果表明，在肝纤维化形成过程中骨桥蛋白表达增加。此外，骨桥蛋白缺陷小鼠对CCl4处理更敏感，在初始阶段表现出更多坏死（可能由于一氧化氮产生不足），随后出现更多纤维化。在肝纤维化形成过程中观察到的骨桥蛋白表达增加可能起到保护作用。
