Issue |
Vet. Res.
Volume 41, Number 1, January-February 2010
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|
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Number of page(s) | 14 | |
DOI | https://doi.org/10.1051/vetres/2009050 | |
Published online | 03 September 2009 | |
How to cite this article | Vet. Res. (2010) 41:02 |
DOI: 10.1051/vetres/2009050
Signaling pathways involved in liver injury and regeneration in rabbit hemorrhagic disease, an animal model of virally-induced fulminant hepatic failure
Rodrigo García-Lastra1, Beatriz San-Miguel2, Irene Crespo2, Francisco Jorquera2, Marcelino Alvarez1, Javier González-Gallego2 and María J. Tuñón21 Department of Animal Health, University of León, 24071 León, Spain
2 Institute of Biomedicine and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), University of León, 24071 León, Spain
Received 3 June 2009; accepted 2 September 2009; published online 03 September 2009
Abstract - Management of fulminant hepatic failure (FHF) continues to be
one challenging problem, and
experimental animal models resembling its clinical conditions are still
needed. Rabbit hemorrhagic disease
(RHD) fullfils many requirements of an animal model of FHF. This work
investigated changes in MAPK,
NF-B, AP-1 and STAT pathways during RHD-induced liver injury. Rabbits were
infected with 2
104
hemagglutination units of an RHD virus isolate. Apoptosis was documented by
the presence of caspase-3
activity and substantial PARP proteolysis at 36 and 48 h postinfection (pi).
Infection induced a marked and
maintained expression of TNF-
from 12 h pi, while there was only a
transitory increase in IL-6 expression.
Expression of phosphorylated (p)-JNK, p-p38 and p-ERK1/2 was significantly
elevated at 12 h pi. At 48 h
pi p-JNK expression was maintained at a maximum level, while that of p-p38
returned to normality and
there was no p-ERK1/2 expression. Activation of NF-
B and AP-1 and increased
expression of VCAM-1
and COX-2 were observed. No significant changes were detected in activation
of STAT1 and STAT3, while
SOCS3 expression increased significantly. The current findings suggest that
activation of JNK is an essential
component in liver injury mediated by the RHD virus and that lack of
activation of STAT3, probably
mediated by SOCS3 over-expression, would contribute to the inhibition of the
regenerative response. Data
show the presence of molecular mechanisms contributing to liver damage and
the lack of regeneration and
they support the usefulness of this model to investigate novel therapeutical
modalities in FHF.
Key words: rabbit hemorrhagic disease / fulminant hepatic failure / mitogen-activated protein kinase / nuclear factor kappa B / signal transducer and activator of transcription
Corresponding author: mjtung@unileon.es
© INRA, EDP Sciences 2009