Role of heparin-binding epidermal growth factor–like growth factor as a hepatotrophic factor in rat liver regeneration after partial hepatectomy

✍ Scribed by Shinichi Kiso; Sumio Kawata; Shinji Tamura; Shigeki Higashiyama; Nobuyuki Ito; Hirofumi Tsushima; Naoyuki Taniguchi; Yuji Matsuzawa

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 887 KB
• Volume: 22
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840220535

✦ Synopsis

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.