title: Hepatoma-derived growth factor is a neurotrophic factor harbored in the nucleus.
abstract: 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.
authors.affiliation: Department of Neurology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Zhou
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Fuminobu
authors.initials: F
authors.lastname: Sugai
authors.forename: Kenya
authors.initials: K
authors.lastname: Yoshida
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Kishima
authors.forename: Hisae
authors.initials: H
authors.lastname: Sumi
authors.forename: Hideji
authors.initials: H
authors.lastname: Nakamura
authors.forename: Saburo
authors.initials: S
authors.lastname: Sakoda
mesh_terms: 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
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009414:Nerve Growth Factors; D012333:RNA, Messenger; C051610:hepatoma-derived growth factor; D025741:HMGA1a Protein