Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Hepatitis B virus suppresses the secretion of insulin-like growth factor binding protein 1 to facilitate anti-apoptotic IGF-1 effects in HepG2 cells

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Human myotubularin-related protein 9 regulates ER-to-Golgi trafficking and modulates WNT3A secretion

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. A programmed wave of uridylation-primed mRNA degradation is essential for meiotic progression and mammalian spermatogenesis

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Hepatitis B virus upregulates host microRNAs that target apoptosis-regulatory genes in an in vitro cell model

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Maintenance of EGFR and EGFRvIII expressions in an in vivo and in vitro model of human glioblastoma multiforme

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. The Rac2 GTPase contributes to cathepsin H-mediated protection against cytokine-induced apoptosis in insulin-secreting cells

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Characterization of plasma lipidomics in adolescent subjects with increased risk for type 1 diabetes in the DiPiS cohort

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Long Noncoding RNAs in Diabetes and β-Cell Regulation

    Research output: Chapter in Book/Report/Conference proceedingBook chapterResearchpeer-review

  4. Increased levels of inflammatory factors are associated with severity of polyneuropathy in type 1 diabetes

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Self-reported immunity and opinions on vaccination of hospital personnel among paediatric healthcare workers in Denmark

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

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.

Original languageEnglish
JournalExperimental Cell Research
Volume370
Issue number2
Pages (from-to)399-408
ISSN0014-4827
DOIs
Publication statusPublished - 1 Sep 2018

ID: 54889222