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Abstract

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 β1, β3, and β4 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 β1, α1, α5, α6, and α9 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 β1, α1, α5, and α9 reached levels comparable to those observed in the adult state. α6 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 α1, the marked induction of α6, and the de novo acquisition of the β4, α2, and α3 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 and endothelial cell populations of the liver.