title: Hepatoma-derived growth factor is highly expressed in developing liver and promotes fetal hepatocyte proliferation.
abstract: Hepatoma-derived growth factor (HDGF) is a heparin-binding protein, which has been purified from the conditioned media of HuH-7 hepatoma cells. Recent studies have suggested the involvement of HDGF in development of the kidney and cardiovascular systems. In the present study, we investigated the possibility that HDGF was also involved in liver development. Northern blot and immunostaining revealed unique expression patterns of HDGF in liver development. HDGF expression was strongly detected in the fetal liver of the midgestation stage and was markedly decreased near birth. Its expression was mainly detected in stromal cells, including immature hepatocytes. Expression in hepatocytes decreased with differentiation. Administration of recombinant HDGF enhanced the growth of primary cultured fetal hepatocytes significantly, although the effect was small. The effect of exogenous HDGF on the proliferation of neonatal hepatocytes was also small and significant only at one point, despite the lower expression of endogenous HDGF, suggesting that the differences exist between fetal and neonatal hepatocytes. However, adenoviral introduction of HDGF antisense cDNA into the fetal hepatocytes significantly suppressed their proliferation, and the inhibitory effect of HDGF antisense virus was reversed by exogenous HDGF. In conclusion, HDGF helps regulate the hepatocyte proliferation in liver development.
authors.affiliation: Department of Molecular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hirayuki
authors.initials: H
authors.lastname: Enomoto
authors.forename: Kenya
authors.initials: K
authors.lastname: Yoshida
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Kishima
authors.forename: Taisei
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Mitsunari
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Allen D
authors.initials: AD
authors.lastname: Everett
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyajima
authors.forename: Hideji
authors.initials: H
authors.lastname: Nakamura
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D016375:Antisense Elements (Genetics); D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D005333:Fetus / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D022781:Hepatocytes / Q000166:cytology* / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008099:Liver / Q000166:cytology / Q000196:embryology*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D016375:Antisense Elements (Genetics); D036341:Intercellular Signaling Peptides and Proteins; C051610:hepatoma-derived growth factor