کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3427338 1227385 2006 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Microarray analyses and molecular profiling of Stat3 signaling pathway induced by hepatitis C virus core protein in human hepatocytes
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ویروس شناسی
پیش نمایش صفحه اول مقاله
Microarray analyses and molecular profiling of Stat3 signaling pathway induced by hepatitis C virus core protein in human hepatocytes
چکیده انگلیسی

Hepatitis C virus (HCV) infection is a major contributor to the development of end-stage liver disease, including cirrhosis and hepatocellular carcinoma (HCC). We have previously shown that HCV core protein promotes immortalization of primary human hepatocytes. To identify molecular changes involved in core protein-mediated immortalization, we have investigated differential gene expression by microarray analyses in primary human hepatocytes and HCV core gene introduced hepatocytes after senescence (early passage), immortalization (middle passage), and anchor-independent growth (late passage). Out of 33,000 human genes screened, 1918 transcripts were differentially expressed (>2-fold) in immortalized human hepatocytes (IHH) as compared to negative controls. Our analyses provided a molecular portrait of changes in gene expression associated with three distinct stages of hepatocytes after introduction of HCV core gene. Many of the overall changes were involved with important cellular pathways, including cell growth regulation, immune regulation, oxidative stress, and apoptosis. We focused on the Stat3 signaling pathway by further verifying selected genes at the protein level relevant to hepatocyte growth regulation. Our data suggested that the introduction of HCV core protein results in an increase in expression of IL-6, gp130, leptin receptor, and Stat3. Upregulation of these genes in turn may regulate c-myc and cyclin D1, downstream of the Stat3 signaling pathway. Identification of these modulated genes with potential roles may help in the selection of targets for therapies against HCV-mediated liver disease progression.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Virology - Volume 349, Issue 2, 5 June 2006, Pages 347–358
نویسندگان
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