Article

Study of the expression levels of Hepatocyte nuclear factor 4 alpha and 3 beta in patients with different outcome of HBV infection.

Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, Sichuan Province, People's Republic of China.
Virology Journal (impact factor: 2.34). 01/2012; 9:23. DOI:10.1186/1743-422X-9-23 pp.23
Source: PubMed

ABSTRACT Hepatocyte nuclear factors 4 alpha (HNF4α) and 3 beta (HNF3β) are members of a group of liver-enriched transcription factors (LETFs) that play important roles in regulating the replication of hepatitis B virus (HBV) and liver inflammation. However, the relationship of the level of HNF4α and HNF3β with the severity of HBV-infected liver diseases is unclear. In this study, liver tissue samples from different types of HBV patients were collected, and HNF4α and HNF3β expression were detected by immunohistochemistry. The expression of HNF4α was significant higher in patients with severe hepatitis B(SHB) than those with chronic hepatitis B(CHB) and liver cirrhosis(LC) (both P < 0.05), but similar between patients with CHB and LC (P > 0.05). And the expression of HNF3β was similar among patients with CHB, LC and SHB (P > 0.05 for all pairwise comparison). This suggests that the expression level of HNF4α was different in patients with different outcome of HBV infection, high expression level of HNF4α may correlate with occurrence of SHB.

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    Article: Mucroporin-M1 Inhibits Hepatitis B Virus Replication by Activating the Mitogen-activated Protein Kinase (MAPK) Pathway and Down-regulating HNF4 in Vitro and in Vivo *
    Zhenhuan Zhao, Wei Hong, Zhengyang Zeng, Yingliang Wu, Kanghong Hu, Xiaohui Tian, Wenxin Li, Zhijian Cao
    [show abstract] [hide abstract]
    ABSTRACT: Background: Mucroporin-M1 is a scorpion venom-derived peptide. Results: Mucroporin-M1 peptide activates the MAPK pathway, and then reduces the expression of HNF4, resulting in the inhibition of HBV replication in vitro and in vivo. Conclusion: Mucroporin-M1 inhibits HBV replication by activating MAPK pathway and down-regulating HNF4. Significance: New-resourced peptide inhibits HBV replication by a novel mechanism. Hepatitis B virus (HBV) is a noncytopathic human hepadna-virus that causes acute, chronic hepatitis and hepatocellular car-cinoma (HCC). As the clinical utility of current therapies is lim-ited, new anti-HBV agents and sources for such agents are still highly sought after. Here, we report that Mucroporin-M1, a scorpion venom-derived peptide, reduces the amount of extra-cellular HBsAg, HBeAg, and HBV DNA productions of HepG2.2.15 cells in a dose-dependent manner and inhibits HBV capsid DNA, HBV intracellular RNA replication intermediates and the HBV Core protein in the cytoplasm of HepG2.2.15 cells. Using a mouse model of HBV infection, we found that HBV replication was significantly inhibited by intravenous injection of the Mucroporin-M1 peptide. This inhibitory activity was due to a reduction in HBV promoter activity caused by a decrease in the binding of HNF4 to the precore/core promoter region. Furthermore, we confirmed that Mucroporin-M1 could selec-tively activate mitogen-activated protein kinases (MAPKs) and lead to the down-regulation of HNF4 expression, which explains the decreased binding of HNF4 to the HBV promoter. Moreover, when the protein phosphorylation activity of the MAPK pathway was inhibited, both HNF4 expression and HBV replication recovered. Finally, we proved that treatment with the Mucroporin-M1 peptide increased phosphorylation of the MAPK proteins in HBV-harboring mice. These results implicate Mucroporin-M1 peptide can activate the MAPK path-way and then reduce the expression of HNF4, resulting in the inhibition of HBV replication in vitro and in vivo. Our work also opens new doors to discovering novel anti-HBV agents or sources.
    Journal of Biological Chemistry 07/2012; · 4.77 Impact Factor
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Keywords

3 beta
 
chronic hepatitis B(CHB)
 
different outcome
 
expression level
 
HBV
 
HBV infection
 
HBV patients
 
HBV-infected liver diseases
 
hepatitis B virus
 
Hepatocyte nuclear factors 4 alpha
 
HNF3β expression
 
HNF4α
 
liver cirrhosis(LC)
 
liver inflammation
 
liver tissue samples
 
liver-enriched transcription factors
 
pairwise comparison
 
patients
 
severe hepatitis B(SHB)
 
SHB