Expression of integrins during liver organogenesis in humans

Expression of integrins during liver organogenesis in humans
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DOI:
10.1002/hep.510270328
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发表时间:
1998-03-01
期刊:
影响因子:
13.5
通讯作者:
Scoazec, JY
Scoazec, JY
中科院分区:
医学1区
文献类型:
--
作者:
Couvelard, A;Bringuier, AF;Scoazec, JY

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整联蛋白通过介导分化细胞与细胞外基质之间的相互作用,在器官发生中起着关键作用。我们分析了人类肝脏器官发生过程中整联蛋白及其配体的表达情况。通过免疫过氧化物酶法对妊娠5至40周的胎儿肝脏样本研究了β1、β3和β4整联蛋白的表达以及几种细胞外基质蛋白的分布。肝母细胞仅表达β1、α1、α5、α6和α9整联蛋白链。在妊娠第8周出现的胎儿肝细胞最初保留了相同的整联蛋白组合,但它们的表达水平逐渐下降。妊娠15周后,β1、α1、α5和α9的表达水平达到与成人状态下观察到的相当的水平。α6的表达在妊娠30周后无法检测到。与肝母细胞相比,在妊娠第8周在胆管板中分化的肝内胆管上皮细胞的特征是α1逐渐缺失,α6显著诱导,以及新获得β4、α2和α3整联蛋白链。肝细胞上的层粘连蛋白整联蛋白受体的消失与肝窦周基质中层粘连蛋白的稀少有关,而它们在胆管上皮细胞上的诱导与在与胆管板接触点的层粘连蛋白沉积有关。总之,整联蛋白可能在肝脏上皮细胞群的分化中起重要作用。
Integrins play a pivotal role in organogenesis, by mediating the interactions between differentiating cells and the extracellular matrix. We analyzed the expression of integrins and their ligands during human liver organogenesis. The expression of beta 1, beta 3, and beta 4 integrins and the distribution of several extracellular matrix proteins were studied by immunoperoxidase in fetal liver samples from 5 to 40 weeks' gestation. Hepatoblasts expressed only the beta 1, alpha I, alpha 5, alpha 6, and alpha 9 integrin chains. Fetal hepatocytes, emerging at the 8th week of gestation, initially retained the same combination of integrins, but presented a progressive decrease in their expression levels. After 15 weeks' gestation, the expression levels of beta 1, alpha 1, alpha 5, and alpha 9 reached levels comparable to those observed in the adult state. alpha 6 expression became undetectable after 30 weeks' gestation. As compared to hepatoblasts, intrahepatic biliary epithelial cells, differentiating at the 8th week of gestation in the ductal plate, were characterized by the progressive loss of alpha 1, the marked induction of alpha 6, and the de novo acquisition of the beta 4, alpha 2, and alpha 3 integrin chains. The disappearance of integrin receptors for laminin on hepatocytes was associated with the rarefaction of laminin in the perisinusoidal matrix, whereas their induction on biliary epithelial cells was associated with laminin deposition at the point of contact with the ductal plate. In conclusion, integrins likely play an important role in the differentiation of the epithelial cell populations of the liver.