Immunolocalization of extracellular matrix components and integrins during mouse liver development
Immunolocalization of extracellular matrix components and integrins during mouse liver development
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DOI：
10.1002/hep.20303
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发表时间：
2004-08-01
期刊：
影响因子：
13.5
通讯作者：
Sugiyama, Y
中科院分区：
文献类型：
--
作者：
Shiojiri, N;Sugiyama, Y
肝内胆道细胞分化发生在门静脉周围肝母细胞中，受下周结缔组织的影响，其机制尚不清楚。本研究分析了小鼠肝脏发育过程中细胞外基质成分及其细胞受体的免疫定位，特别关注了胆道分化和血管发育。在幼龄胎鼠肝脏中，与造血细胞相关的肝索之间形成了原始的窦状结构，其免疫组化结果显示，这些造血细胞与基底层成分、α 6整合素亚基和PECAM-1有关。门静脉和肝静脉在发育早期就表现出不同程度的α 2、α 3和α 6整合素亚基染色。围产期后，抗- β 4整合素亚基抗体与门静脉发生反应，但与肝静脉不发生反应。它们的不同表型可能与门静脉周围胆管的优先分化有关。在肝内胆管发育过程中，接近结缔组织的门静脉周围肝母细胞几乎同时对基侧各基层流成分进行免疫染色；Alpha3、alpha5、alpha6和beta4整合素亚基的免疫组织化学检测晚于基底层流成分。肝内胆管细胞的染色模式与肝外胆管细胞从发育之初就明显不同，提示这两种胆管的起源不同。综上所述，包括窦、门静脉和肝静脉在内的血管结构在肝脏发育早期就已形成，细胞外基质成分可能在胆道分化和血管发育中起重要作用。
Intrahepatic biliary cell differentiation takes place in periportal hepatoblasts under the influence of the subjacent connective tissue, the mechanism of which is still unclear. This study was undertaken to analyze the immunolocalization of extracellular matrix components and their cellular receptors during mouse liver development, with special attention given to biliary differentiation and vascular development. In young fetal mouse liver, primitive structures of sinusoids were developed between hepatic cords associated with hematopoietic cells demonstrated by immunohistochemistry of basal laminar components, the alpha6 integrin subunit, and PECAM-1. Portal veins and hepatic veins showed different staining intensities of alpha2, alpha3, and alpha6 integrin subunits from early stages of development. Anti-beta4 integrin subunit antibodies reacted with portal veins, but not with hepatic veins after perinatal stages. Their different phenotypes may be related to the preferential differentiation of periportal bile ducts. In intrahepatic bile duct development, periportal hepatoblasts adjacent to the connective tissue were immunostained for each basal laminar component on the basal side at almost the same time; alpha3, alpha5, alpha6, and beta4 integrin subunits were immunohistochemically detectable later than the basal laminar components. These staining patterns of intrahepatic bile duct cells clearly differed from those of extrahepatic bile duct cells from the beginning of their development, suggesting that these ducts are of different origins. In conclusion, the vascular structures, including sinusoids, portal veins, and hepatic veins, develop from early stages of liver development, and the extracellular matrix components may play important roles in biliary differentiation and vascular development.