Suppressive effect on hepatocyte differentiation of hepatitis C virus core protein.
The influence of hepatitis C virus (HCV) protein(s) on cellular differentiation remains to be clarified. Using murine normal liver epithelial cells, we investigated whether HCV core protein affects differentiation into hepatocytes. Mock and HCV core-expressing cells were stimulated with oncostatin M (OSM) and dexamethasone, and the degree of differentiation was evaluated by measuring the expression of albumin and tyrosine aminotransferase (TAT). Lower amounts after stimulation were found in HCV core-expressing cells than in mock cells. Phosphorylation of the signal transducer and activator transcription factor 3 (STAT3) was prevented by the HCV core under OSM stimulation. Reporter gene assay revealed that the HCV core/Janus kinase (JAK) interaction directly suppressed the OSM-dependent JAK-STAT signal transduction. Furthermore, expression of OSM receptor beta (OSMRbeta) after stimulation was prevented by the HCV core. In conclusion, the HCV core may suppress differentiation into hepatocytes via inhibition of the JAK-STAT pathway and OSMRbeta expression.
Hosui
Atsushi
A
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita 565-0871, Japan.
Takehara
Tetsuo
T
Ohkawa
Kazuyoshi
K
Kanazawa
Yoshiyuki
Y
Tatsumi
Tomohide
T
Yamaguchi
Shinjiro
S
Sakamori
Ryotaro
R
Hiramatsu
Naoki
N
Kanto
Tatsuya
T
Hayashi
Norio
N
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D016207:Cytokines / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D016174:Hepacivirus / Q000737:chemistry*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D053683:Oncostatin M; D050796:STAT3 Transcription Factor / Q000502:physiology; D014758:Viral Core Proteins / Q000494:pharmacology*
D016207:Cytokines; C508352:Osm protein, mouse; D050796:STAT3 Transcription Factor; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D053683:Oncostatin M; D003907:Dexamethasone