Hepatitis C virus core protein genotype 3a increases SOCS-7 expression through PPAR-{gamma} in Huh-7 cells.
Hepatitis C virus (HCV) core protein genotype 3a induces the expression of suppressor of cytokine signalling protein 7 (SOCS-7), which is partially involved in the development of insulin resistance. The aim of the present study was to investigate the mechanism through which the core protein regulates SOCS-7 expression. We have explored, in the in vitro model of Huh-7 cells expressing the HCV core protein of genotype 3a, whether the expression of SOCS-7 as well as of other members of the SOCS family (SOCS-1 and SOCS-3) was activated by the STAT3 pathway, using immunoblotting and real-time PCR upon alpha interferon (IFN-alpha) treatment. We found that, whilst IFN-alpha treatment induced STAT3 activation and consequently SOCS-1 and SOCS-3 upregulation in HCV genotype 3a core-expressing Huh-7 cells, SOCS-7 mRNA expression was independent of STAT3 and seemed to be modulated by peroxisome proliferator-activated receptor gamma (PPAR-gamma) activity, as demonstrated by quantitative real-time PCR and immunoblot detection after treatment with the PPAR-gamma agonist rosiglitazone or the PPAR-gamma antagonist GW9262. In contrast to the other studied members of the SOCS family (1 and 3), which are regulated by STAT3 activation, SOCS-7 expression appears to be STAT3-independent and seems to be regulated instead by PPAR-gamma. This is the first report proposing a molecular mechanism through which the HCV core protein (genotype 3a) modulates SOCS-7 expression.
Pazienza
Valerio
V
Gastroenterology Unit, IRCCS 'Casa Sollievo della Sofferenza' Hospital, San Giovanni Rotondo (FG), Italy. v.pazienza@operapadrepio.it
Vinciguerra
Manlio
M
Andriulli
Angelo
A
Mangia
Alessandra
A
D000998:Antiviral Agents; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000502:physiology; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D014758:Viral Core Proteins / Q000145:classification / Q000235:genetics*
D000998:Antiviral Agents; D009687:Nuclear Proteins; D047495:PPAR gamma; C108775:SOCS7 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050826:Suppressor of Cytokine Signaling Proteins; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus