کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8949713 | 1645722 | 2018 | 27 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Hepatitis B virus suppresses the secretion of insulin-like growth factor binding protein 1 to facilitate anti-apoptotic IGF-1 effects in HepG2 cells
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کلمات کلیدی
IGFBP1HepG2STSHBV X proteinCHBIGF-1HBxThapsigarginHBSHCC - HCCstaurosporine - استوسوسورپینApoptosis - خزان یاختهایinsulin-like growth factor 1 - فاکتور رشد مانند انسولین 1chronic hepatitis B - هپاتیت B مزمن، هپاتیت ب مزمنHBV - هپاتیت بhepatitis B virus - ویروس هپاتیت بیInsulin-like growth factor binding protein 1 - پروتئین اتصال دهنده فاکتور رشد مانند انسولین 1Hepatocellular carcinoma - کارسینوم هپاتوسلولار(کارسینوم سلولهای استخوانی)
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
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چکیده انگلیسی
Hepatitis B virus (HBV) infection is a major global health burden as chronic hepatitis B (CHB) is associated with the development of liver diseases including hepatocellular carcinoma (HCC). To gain insight into the mechanisms causing HBV-related HCC, we investigated the effects of HBV replication on global host cell gene expression using human HepG2 liver cells. By microarray analysis, we identified 54 differentially expressed genes in HBV-replicating HepG2 cells. One of the differentially-expressed genes was insulin-like growth factor binding protein 1 (IGFBP1) which was downregulated in HBV-replicating cells. Consistent with the gene expression data, IGFBP1 was suppressed at both the cellular and secreted protein levels in the presence of HBV replication. Transient transfection experiments with an inducible plasmid encoding the HBV X protein (HBx) revealed that HBx alone was sufficient to modulate IGFBP1 expression. Small interference RNA (siRNA)-mediated loss of function studies revealed that knockdown of IGFBP1 reduced apoptosis induced by either thapsigargin (TG) or staurosporine (STS). Treatment of cells with recombinant insulin-like growth factor 1 (IGF-1) decreased both TG- or STS-induced apoptosis. Interestingly, addition of recombinant IGFBP1 reversed the anti-apoptotic effect of IGF-1 on TG-induced, but not STS-induced, apoptosis. In conclusion, our results suggest an anti-apoptotic autocrine function of HBV-mediated downregulation of IGFBP1 in HepG2 cells. Such an effect may contribute to the development of HBV-mediated HCC by increasing pro-survival and anti-apoptotic IGF-1 effects.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 370, Issue 2, 15 September 2018, Pages 399-408
Journal: Experimental Cell Research - Volume 370, Issue 2, 15 September 2018, Pages 399-408
نویسندگان
Kirstine Overgaard Nielsen, Aashiq Hussain Mirza, Simranjeet Kaur, Kari Stougaard Jacobsen, Thilde Nordmann Winther, Dieter Glebe, Flemming Pociot, Birthe Hogh, Joachim Størling,