Author/Authors :
Arends، نويسنده , , Brigitte and Spee، نويسنده , , Bart and Hoffmann، نويسنده , , Gaby and Jansen، نويسنده , , Georgina E.G. and Slump، نويسنده , , Estel and Auriemma، نويسنده , , Edoardo and IJzer، نويسنده , , Jooske and Hemrika، نويسنده , , Wieger and Romijn، نويسنده , , Roland A. and van der Heijden-Liefkens، نويسنده , , Karin H.A. and Sondermeijer، نويسنده , , Paul J.A. and van den Ingh، نويسنده , , Ted S.G.A.M. and Penning، نويسنده , , Louis C. and Rothuizen، نويسنده , , Jan، نويسنده ,
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.
ro 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 7 days 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.
Keywords :
Partial hepatectomy , ERK1/2 , PCNA , Liver regeneration , Dogs , HGF , PKB , c-Met
