In vitro and in vivo bioactivity of recombinant canine hepatocyte growth factor

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 expr...

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Veröffentlicht in:The veterinary journal (1997) 2008-10, Vol.178 (1), p.70-77
Hauptverfasser: 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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container_end_page 77
container_issue 1
container_start_page 70
container_title The veterinary journal (1997)
container_volume 178
creator 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
description 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 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.
doi_str_mv 10.1016/j.tvjl.2007.11.002
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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 7 days after phx. 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subjects Animals
apoptosis
bioactive properties
biochemical pathways
c-MET
Cell Line
dog diseases
Dogs
epithelial cells
ERK1/2
excision
Extracellular Signal-Regulated MAP Kinases - genetics
Extracellular Signal-Regulated MAP Kinases - metabolism
Female
Gene Expression Regulation - drug effects
Hepatectomy
hepatocyte growth factor
Hepatocyte Growth Factor - genetics
Hepatocyte Growth Factor - metabolism
Hepatocytes - drug effects
HGF
in vitro studies
in vivo studies
liver
Liver - drug effects
Liver - physiology
liver diseases
Liver regeneration
Liver Regeneration - drug effects
mitosis
oncogenes
Organ Size
Partial hepatectomy
PCNA
phosphorylation
physiological response
PKB
Proto-Oncogene Proteins c-akt - genetics
Proto-Oncogene Proteins c-akt - metabolism
Proto-Oncogene Proteins c-met - genetics
Proto-Oncogene Proteins c-met - metabolism
Recombinant Proteins
title In vitro and in vivo bioactivity of recombinant canine hepatocyte growth factor
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