TY - JOUR
T1 - Hepatoma-derived growth factor is highly expressed in developing liver and promotes fetal hepatocyte proliferation
AU - Enomoto, Hirayuki
AU - Yoshida, Kenya
AU - Kishima, Yoshihiko
AU - Kinoshita, Taisei
AU - Yamamoto, Mitsunari
AU - Everett, Allen D.
AU - Miyajima, Atsushi
AU - Nakamura, Hideji
N1 - Funding Information:
Abbreviations: E, embryonic day; AFP, α-fetoprotein; HDGF, hepatoma-derived growth factor; TAT, tyrosine amino transferase; OSM, oncostatin M; EGFP, enhanced green fluorescence protein; MOI, multiplicity of infection. From the 1Department of Molecular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan; 2Laboratory of Cellular Biosynthesis, Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan; and 3Department of Pediatrics, University of Virginia Health Science Center, Charlottesville, VA. Received February 19, 2002; accepted September 7, 2002. Supported in part by a Grant-in-Aid for Scientific Research of the Ministry of Education, Culture, Sports, Science, and Technology of Japan. T.K.’s current address is RIGEL Inc., 240 East Grand Avenue, South San Francisco, CA 94080. Address reprint requests to: Hideji Nakamura, Department of Molecular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamada-oka Suita, Osaka 565-0871, Japan. E-mail: nakamura@imed3.med.osaka-u.ac.jp; fax: (81) 6-6879-3839. Copyright © 2002 by the American Association for the Study of Liver Diseases. 0270-9139/02/3606-0028$35.00/0 doi:10.1053/jhep.2002.36935
PY - 2002/12/1
Y1 - 2002/12/1
N2 - 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.
AB - 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.
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U2 - 10.1053/jhep.2002.36935
DO - 10.1053/jhep.2002.36935
M3 - Article
C2 - 12447878
AN - SCOPUS:0036895940
SN - 0270-9139
VL - 36
SP - 1519
EP - 1527
JO - Hepatology
JF - Hepatology
IS - 6
ER -