Expression of AFP and Rev-Erb A/Rev-Erb B and N-CoR in fetal rat liver, liver injury and liver regeneration

The expression of AFP gene and orphan nuclear receptors in the liver was examined in different rat models: (a) fetal liver (b) liver regeneration [partial hepatectomy (PH) with and without 2-acetyl-aminofluren treatment (2-AAF)], (c) acute liver damage [treatment with CCl4] and (d) acute phase reaction [treatment with turpentine oil]. After PH of 2-AAF treated rats, clusters of AFP positive cells occurred in the periportal region. In the Northern blot analysis, a positive hybridization signal for the full-length AFP-RNA was observed only in liver samples from 2-AAF treated rats after PH. In real-time PCR analysis, the full-length AFP-RNA was highly up regulated in the fetal liver (maximum at day 14: 21,500 fold); after PH of 2-AAF treated rats, the full-length AFP-RNA was also up regulated up to 400 fold (day 7 after PH). The orphan nuclear receptors were down regulated at nearly each time points in all models, also at time point of up regulation of the AFP gene.Expression of "fetal" AFP could be demonstrated during liver development and during proliferation of the so-called oval cells. Changes of expression of orphan nuclear receptors, however, did not correlate with AFP expression. Other regulatory pathways were possibly involved in controlling AFP expression, in vivo.During severe and chronic liver damage, a subpopulation of liver cells termed oval cells was induced to proliferate. The oval cells are not typical hepatocytes; they are indeed less mature cells that can function as progenitors for either hepatocytic or ductal cell lineages. This kind of cells express alpha-fetoprotein (AFP) transcripts [1-3]. AFP is an oncofetal gene, which occurs at high rate in the yolk sac, fetal liver and intestine; but is otherwise shut off in the first weeks after birth [4,5]. In the adult liver, AFP is expressed in only very small amounts; nonetheless, AFP expression can resume in certain pathophysiological situations, such as liver regeneration (e.g., after surgical resectio