Abstract. To analyze at the cellular level the decrease in alpha-fetoprotein (AFP) gene expression during the early postnatal growth, we searched for AFP gene transcripts by in situ hybridization using a specific cDNA probe, and for the corresponding protein by immunocytochemistry, on rat liver sections at various times of the perinatal period. The relative number of mRNA sequences was evaluated by Northern blot analysis. Albumin (ALB) gene expression was studied simultaneously with the same techniques.In 17-19-d-old fetuses all hepatocytes express simultaneously, for both genes, the mRNAs and the corresponding proteins. During the first postnatal weeks, at a time when the global number of AFP mRNA molecules decreases, all hepatocytes still contain cytoplasmic transcripts and protein. A zonal heterogeneity in the level of AFP gene expression develops around the first week, a higher number of gene products being detected in perivenous than in periportal hepatocytes. This heterogeneity persists until the fourth week when AFP mRNA sequences and protein are barely detectable. All hepatocytes express the ALB gene after birth, but at around the second week, a periportal intensification of the in situ hybridization signal and immunostaining becomes apparent. Our data indicate that (a) co-expression of the AFP and ALB genes by all hepatocytes is a normal step in liver ontogeny; (b) the diminution of AFP gene expression after birth is not the result of the disappearance of specialized cell clones; and (c) zonal quantitative differences in the level of AFP and ALB gene expression are observed within the maturing liver lobule.
ABSTRACT— Nuclear protooncogene and alpha‐fetoprotein gene expression is stimulated in hepatocytes during liver regeneration and by various growth factors in vitro. Metabolic adaptation of hepatocytes has been implicated in such gene reprogrammation. We examine here whether induction of an acute inflammation, a physiological situation of important metabolic adjustments, also triggers activation of nuclear oncogenes and of the AFP gene in rat liver. C‐fos, c‐jun and c‐myc mRNA accumulated on Northern blots between 4–12 h of inflammation and the steady‐state level of two small alpha‐fetoprotein transcripts characteristic of the adult liver increased at 4 h and 24 h of inflammation. In situ hybridization showed accumulation of the mRNA of the four genes studied in all hepatocytes, without any zonal lobular heterogeneity. 3H‐histoautoradiography and mitotic counts indicated an inhibition of DNA synthesis and mitosis, prolonged for at least 48 h after inflammation. Thus acute inflammation triggers the activation of nuclear protooncogenes and alpha‐fetoprotein gene in hepatocytes, but this activation is not followed by passage into the replicative cycle.
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