Hepatoma-derived growth factor is a neurotrophic factor harbored in the nucleus.
Hepatoma-derived growth factor (HDGF) is a heparin-binding proliferating factor originally isolated from conditioned medium of the hepatoma-derived cell line HuH-7. HDGF has greatest homology in an amino acid sequence with high mobility group 1 (HMG1), which has been characterized as a DNA-binding, inflammatory, and potent neurite outgrowth molecule. HDGF is reported to be widely expressed and act as a growth factor in many kinds of cells. However, it has not been investigated in the nervous system. Here, we show by Western blot analysis that HDGF is present in the mouse brain from the embryonic period until adulthood. In situ hybridization and immunohistochemical analyses revealed that HDGF was expressed mainly in neurons, and HDGF protein was localized to the nucleus. HDGF and high mobility group 1 were secreted under physiological conditions and released extracellularly in necrotic conditions. Furthermore, we showed that exogenously supplied HDGF had a neurotrophic effect and was able to partially prevent the cell death of neurons in which endogenous HDGF was suppressed. Therefore, we propose that HDGF is a novel type of neurotrophic factor, on account of its localization in the nucleus and its potential to function in an autocrine manner under both physiological and pathological conditions throughout life.
Zhou
Zhiwei
Z
Department of Neurology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
Yamamoto
Yoichi
Y
Sugai
Fuminobu
F
Yoshida
Kenya
K
Kishima
Yoshihiko
Y
Sumi
Hisae
H
Nakamura
Hideji
H
Sakoda
Saburo
S
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D019898:Autocrine Communication; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D025741:HMGA1a Protein / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis
D036341:Intercellular Signaling Peptides and Proteins; D009414:Nerve Growth Factors; D012333:RNA, Messenger; C051610:hepatoma-derived growth factor; D025741:HMGA1a Protein