| Previous, several laboratories have demonstrated the presence of a hepatic-cytosolic stimulator in regenerating liver and human fetal liver. The ALR mRNA encoding an open reading frame of 484 amino acids 125 amino acid was isolated from newborn mouse in 1994 by Hagiya and its molecular weight is 15 kd. The size of ALR protein determined by Western Wot argues for different translation products. Two major 2.3 and 3.0 kd bands were visible in rat liver which suggest the possibility that the rat ALR is physiologically a homodimer. Recently, the 1.3 and 2.7 kb bands visible in the Northern blot indicated the ALR gene may have multiple translational initiation sites, or alternatively, ALR protein may be processed by a post-transcriptional mechanism. Yang et al. identified hepatic stimulatory activity in fraction with molecular size ranging from 10 to 30 kDa of human fetal liver lysate and the factor was named as hepatopoietin (HPO). Later they proved that HPO is encoded by mRNA of human fetal liver and further cloned its full-length cDNA, encoding a 15.1-Kda protein from the cDNA library of human fetal liver, which is of 87% homology with rat augmenter of liver regeneration (ALR) cDNA and is identical to the human homologue of yeast ERV1. Recombinant human hepatopoietin (rhHPO) showed its activity on specifically stimulating DNA synthesis of hepatic cells and promoting healing after liver injury in vitro and in vivo.Recently, HPO/ALR/EVR1 homologous cDNAs (including EST sequences) have been isolated in many laboratories. Sequence analysis of these homologous cDNAs revealed that the same 3' sequence was presented in all reportedsequences, however, the 5' sequence varied in these cDNAs. Furthermore, The analysis of genomic sequences of HPO/ALR also suggest that maybe exist different transcripts in nature.A novel transcript of human HPO (HPO-205) encoding a 205 amino acid ORF corresponding to a translated production of 23 kDa was isolated from human fetal liver cDNA library by S'-race methods and distinguished from the previous HPO that lacks the N-terminal 80 amino acids. The dose-dependent stimulation of DNA synthesis of HepG2 hepatoma cells by HPO-205 demonstrated its similar biological activity with HPO in vitro. We further examined the level of MAPK (Mitogen-activated protein kinase) phosphorylation by Western blot analysis and the result revealed that HPO-205 protein might have the stronger activity on stimulating hepatic cell proliferation than that of HPO. The similar result was observed by FACS technique. So, the primary biological function of HPO-205 has demonstrated that the comparison of HPO-205 and HPO will lead to a new insight of studying the structure and function of HPO, and provided the new way of thinking to deeply elucidate the biological roles of HPO.The sustained production of large number of hematopoietic cell is theorized being maintained by a small population of pluripotential hematopoietic stem cells during vertebrate ontogeny. The major anatomic site of hematopoiesis in mammal switches from the yolk sac and paraortic nodes, migrates to the liver and spleen, and finally lodges in the bone marrow, which remains hematopoietic throughout life. Liver hematopoiesis is detectable in the mouse by day 10 and in human by week 6 of gestation, and the liver is the major hemopoietic organ during fetal life until the first postnatal week. It has been reported that about 1% of genes are differentially expressed between fetal and adult liver. While adult liver is nearly free of hematopoietic function, the 10-12 week fetal liver is comprised of 80% hematopoietic cells. The ability of the liver to change its function so abruptly provides a fascinating and import model with which to study the molecular regulation of both normal and abnormal cell growth and differentiation. Thus, it is important to distinguish genes that are selectively induced in fetal liverhematopoietic cells for understanding the molecular mechanisms of hematopoietic development.A novel gene, named EDAG and abundan...
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