ArticleLipids in health and disease2016
The mechanism of apoliprotein A1 down-regulated by Hepatitis B virus.
Article in Lipids in health and disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27 citing papers in PubMed, 40 citations in OpenAlex.
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- Small hepatitis B virus surface antigen (SHBs) induces dyslipidemia by suppressing apolipoprotein-AII expression through ER stress-mediated modulation of HNF4α and C/EBPγ.Journal of virology · 2024Article
- Comprehensive review and updated analysis of DNA methylation in hepatocellular carcinoma: From basic research to clinical application.Clinical and translational medicine · 2024Review
- System Biology Investigation Revealed Lipopolysaccharide and Alcohol-Induced Hepatocellular Carcinoma Resembled Hepatitis B Virus Immunobiology and Pathogenesis.International journal of molecular sciences · 2023Article
- SARS-CoV-2 induced HDL dysfunction may affect the host's response to and recovery from COVID-19.Immunity, inflammation and disease · 2023Review
- The Role of Ferroptosis and Cuproptosis in Curcumin against Hepatocellular Carcinoma.Molecules (Basel, Switzerland) · 2023Article
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- Many Ways to Communicate-Crosstalk between the HBV-Infected Cell and Its Environment.Pathogens (Basel, Switzerland) · 2022Review
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- A Novel Cognition of Decitabine: Insights into Immunomodulation and Antiviral Effects.Molecules (Basel, Switzerland) · 2022Review
- Review
- Endosomal Cholesterol in Viral Infections - A Common Denominator?Frontiers in physiology · 2021Review
- Multifaceted Interaction Between Hepatitis B Virus Infection and Lipid Metabolism in Hepatocytes: A Potential Target of Antiviral Therapy for Chronic Hepatitis B.Frontiers in microbiology · 2021Review
- Low APOA-1 Expression in Hepatocellular Carcinoma Patients Is Associated With DNA Methylation and Poor Overall Survival.Frontiers in genetics · 2021Article
- Introducing APOA1 as a key protein in COVID-19 infection: a bioinformatics approach.Gastroenterology and hepatology from bed to bench · 2020Article
- Expression and significance of urinary microRNA in patients with chronic hepatitis B.Medicine · 2019Article
- Serum apolipoprotein C3 levels are negatively associated with hepatitis B virus DNA in HBeAg-negative chronic hepatitis B patients.Lipids in health and disease · 2019Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHepatitis B virus (HBV) infection correlated with the development of cirrhosis, liver failure and hepatocellular carcinoma (HCC), poses a huge health burden on the global community. However, the pathogenesis of chronic hepatitis B (CHB) remains unclear. Apolipoprotein A1 (ApoA1) mainly secreted by hepatocytes, represents the major protein component of high-density lipoprotein. ApoA1 secretion may be disrupted by HBV infection. In this study, we mainly investigated the molecular mechanism of ApoA1 down regulated by HBV for revealing the pathogenesis of CHB.
methodsApoA1 expression in livers of CHB patients as well as healthy controls were performed by Real-time PCR (RT-PCR) and Western blot. The serum ApoA1 levels were measured by Enzymed-linked immunosorbent assay (ELISA). Expression of ApoA1 mRNA and protein levels were performed by RT-PCR and Western blot in human hepatoma HepG2 cells and subline HepG2.2.15 cells. HBV expression construct, pHBV1.3 were transfected into HepG2, the changes of ApoA1 mRNA and protein expression were detected by RT-PCR and Western blot. To further study the mechanism of ApoA1 down regulation by HBV, 11 CpG islands in ApoA1 promotor were tested for DNA methylation status by MSP. HepG2.2.15 cell lines were treated with DNA methyltransferase inhibitor 5-aza-deoxycytidine (5-aza-dC), then, expression of ApoA1 mRNA and HBV particles in the supernatant, as well as ApoA1 protein levels were detected by RT-PCR and Western blot. Secretion of HBsAg and HBeAg in HepG2 cells cotransfected with pApoA1 and pHBV1.3 constructs was tested by ELISA. Meanwhile, secretion of HBsAg and HBeAg in the supernatant were quantified by ELISA in the HepG2.2.15 cells treated with 5-aza-dC plus ApoA1 siRNA.
resultsExpression of ApoA1 mRNA and protein levels, as well as serum ApoA1 levels in CHB patients were decreased corresponding healthy controls in vivo. In addition, the expression of ApoA1 mRNA and protein levels were down regulated in HepG2.2.15 cells correponding HepG2 cells, 11 CpG islands in ApoA1 promoter were tested for methylation status by MSP in HepG2.2.15 cells compared to HepG2 cells, while two CpG islands were found hypermethylated. Expression of ApoA1 mRNA and protein levels were increased in HepG2.2.15 cells treated with DNA methyltransferase inhibitor 5-aza-dC. Furthermore, overexpression of ApoA1 can enhance HBV expression in HepG2 cells while the inhibitory effect of 5-aza-dC on HBV expression was completely abolished by blocking 5-aza-dC-induced up-regulation of ApoA1 using RNAi.
conclusionsEpigenetic silencing of ApoA1 gene expression by CpG island DNA hypermethylation induced by HBV may contribute to the pathogenesis of CHB.
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