In vitro and in vivo bioactivity of recombinant canine hepatocyte growth factor |
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| Authors: | Arends Brigitte Spee Bart Hoffmann Gaby Jansen Georgina E G Slump Estel Auriemma Edoardo Ijzer Jooske Hemrika Wieger Romijn Roland A van der Heijden-Liefkens Karin H A Sondermeijer Paul J A van den Ingh Ted S G A M Penning Louis C Rothuizen Jan |
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| Institution: | Faculty of Veterinary Medicine, Department of Clinical Sciences of Companion Animals, Utrecht University, Yalelaan 104, 3584 CM Utrecht, the Netherlands. |
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| Abstract: | Hepatocyte growth factor (HGF) is crucial for the development and regeneration of the liver and offers a possible new therapeutic strategy for the treatment of canine liver disease. In this study, the in vitro and in vivo bioactivity of recombinant canine HGF (rcHGF) produced with a baculoviral expression system in insect cells was measured. In vitro rcHGF induced mitogenesis, motogenesis, and phosphorylated the HGF receptor c-MET and its downstream mediators PKB and ERK1/2 in two canine epithelial cell lines. After a partial hepatectomy (phx) in dogs, rcHGF increased phosphorylation of c-MET, PKB and ERK1/2. A moderate increase was seen with the cell cycle protein PCNA in rcHGF treated livers, but no HGF-induced increase in liver weight was seen 7 days after phx. Furthermore, rcHGF treated livers showed lower levels of the key mediator of apoptosis, caspase-3, at 7days after phx. It is concluded that rcHGF is a biologically active protein in vitro and in vivo and the baculoviral expression system supplies sufficient amounts of rcHGF for future clinical studies in dogs. |
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