Hepatitis C virus core protein upregulates the transcription of PCK1 through FOXO1/PGC-1α pathway

Abstract:

Abstract:［Objective］We analyzed the effect of the stable expressed Hepatitis C virus core protein on PCK1 mRNA expression level and the molecular mechanisms involved in Huh7-lunet cells．［Methods］A retroviral vector mediated mammalian cell expression cell line of the HCV core protein was constructed． The mRNA and protein levels of PCK1，FOXO1 and PGC-1α were analyzed by Real-time PCR and luciferase assay in Huh7-lunet-core cells． ［Results］ HCV CORE upregulated the mRNA levels of PCK1 significantly． Both the mRNA and protein levels of FOXO1 were not affected in Huh7-lunet-core cells，whereas a decreased phosphorylation status of FOXO1 was exhibited． Moreover，activation of FOXO1 by HCV CORE was detected． Further，the mRNA level of PGC-1α was found to be significantly elevated in Huh7-lunet-core cells．［Conclusion］Our results revealed for the first time that HCV core protein expression-mediated FOXO1 activation and the increased PGC-1α leaded to the elevation of PCK1 at the mRNA level，which suggesting the immoderate gluconeogenesis in HCV-infected hepatocytes． Our findings contributed to the understanding of the molecular mechanisms of HCV-related insulin resistance and provided potential new clues for the prevention and therapy of diabetes．

Key words:Keywords: HCV，CORE，Type 2 diabetes，Insulin resistance，PCK1，Gluconeogenesis，FOXO1，PGC-1α