title: Role of heparin-binding epidermal growth factor-like growth factor as a hepatotrophic factor in rat liver regeneration after partial hepatectomy.
abstract: Several growth factors including hepatocyte growth factor (HGF) have been implicated in the regulation of liver regeneration. Recently, we reported that heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) has hepatotrophic effects in vitro. We investigated the role of HB-EGF as a hepatotrophic factor in regenerating rat liver after 70% partial hepatectomy. The level of HB-EGF messenger RNA (mRNA) in regenerating rat liver increased 1.5 hours after partial hepatectomy and reached a maximum (about sevenfold over normal) at 6 hours. In contrast, hepatic HGF mRNA levels increased at 12 hours and achieved maximal expression at 24 hours. HB-EGF protein expression increased about 2.8-fold over normal at 10 hours after partial hepatectomy. The number of EGF receptors, to which HB-EGF binds, decreased 6 hours after partial hepatectomy. HB-EGF mRNA levels increased in nonparenchymal cells (NPCs) at 6 hours after partial hepatectomy but not in hepatocytes. Using the reverse transcription-polymerase chain reaction (RT-PCR), HB-EGF gene expression was increased predominantly in Kupffer cells and sinusoidal endothelial cells but not in lipocytes and hepatocytes. These results indicated that HB-EGF may be an important growth factor, produced in an earlier phase rather than HGF, in the regenerating liver after partial hepatectomy by a paracrine mechanism.
authors.affiliation: Second Department of Internal Medicine, Osaka University Medical School, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kiso
authors.forename: S
authors.initials: S
authors.lastname: Kawata
authors.forename: S
authors.initials: S
authors.lastname: Tamura
authors.forename: S
authors.initials: S
authors.lastname: Higashiyama
authors.forename: N
authors.initials: N
authors.lastname: Ito
authors.forename: H
authors.initials: H
authors.lastname: Tsushima
authors.forename: N
authors.initials: N
authors.lastname: Taniguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuzawa
mesh_terms: D000818:Animals; D001483:Base Sequence; D004815:Epidermal Growth Factor / Q000502:physiology*; D066246:ErbB Receptors / Q000502:physiology; D015870:Gene Expression; D066257:Heparin-binding EGF-like Growth Factor; D006498:Hepatectomy; D017228:Hepatocyte Growth Factor / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor; D066246:ErbB Receptors