Hepatitis B virus X protein up-regulates tumor necrosis factor-α expression in cultured mesangial cells via ERKs and NF-κB pathways

Lu, Hongzhu; Zhou, Jianhua

doi:10.1016/s2221-1691(13)60053-2

Cited by 10 publications

(6 citation statements)

References 26 publications

(32 reference statements)

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“…HBx is considered the most important determinant in viral pathogenesis (22,23); it is a necessary transcription factor for HBV replication, having an trans-activation effect, which can promote viral replication and induce apoptosis directly, and subsequently induce the occurrence of an inflammatory reaction and serve an important role in cell transformation and proliferation (24,25). Due to the widely trans-activation properties of the HBx gene and its effect on glomerular foot cells, mesangial cells and renal tubule epithelial cells (26)(27)(28)(29), it is considered to have an important role in the pathogenesis of HBV-GN (28,29). A previous study by Zhang et al (15) demon-15) demon-) demonstrated that podocyte number was significantly decreased in the glomeruli of children with HBV-GN, while HBx protein was visualized within the glomerulus in 71% children with HBV-GN, where the expression of HBx protein was localized mainly in the cytoplasm of podocytes, with lower expression in the nuclei of the podocytes (19).…”

Section: Discussionmentioning

confidence: 99%

Hepatitis�B virus X protein decreases nephrin expression and induces podocyte apoptosis via activating STAT3

et al. 2019

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The gene for hepatitis B virus X protein (HBx) comprises the smallest open reading frame in the HBV genome, and the protein product can activate various cell signaling pathways and regulate apoptosis, among other effects. However, in different cell types and under different external conditions, its mechanism of action differs. In the present study, the effect of HBx on the viability and apoptosis of mouse podocyte clone 5 (MPC5) cells was investigated. The cells were transfected with the HBx gene using pEX plasmid, and real-time quantitative PCR and western blot analysis were used to test the transfection efficiency and assess related protein expression. The highest expression of HBx occurred at 48 h after MPC5 cells were transfected with HBx. The expression of nephrin protein in the HBx transfection group was lower than that in blank and negative control groups. Following transfection of the HBx gene, podocyte viability was suppressed, while the rate of cell apoptosis was increased; moreover, the expression of signal transducer and activator of transcription 3 (STAT3) and phospho-STAT3 was increased compared with in the control groups. The present study suggests that STAT3 activation may be involved in the pathogenic mechanism of renal injuries caused by HBV injection. Thus STAT3 is a potential molecular target in the treatment of HBV-GN.

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Section: Discussionmentioning

confidence: 99%

Hepatitis�B virus X protein decreases nephrin expression and induces podocyte apoptosis via activating STAT3

et al. 2019

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“…HBV X gene can activate relevant transcription factors (e.g. ERKs and NF-κB) and upregulate the expression of cell proliferation-associated cytokine TNF-α, further promoting mesangial cell proliferation (Lu et al, 2013). HBX protein can block cyclin B1 degradation and simultaneously downregulate the expression of cyclin A, but upregulate the expression of negative regulatory protein of GAT →GCT Asp88Ala…”

Section: Discussionmentioning

confidence: 99%

Significance of mutations in hepatitis B virus X gene for the pathogenesis of HB-associated glomerulonephritis

Hui¹,

Yan²,

Wei³

et al. 2014

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“…TNF is a pleiotropic cytokine that exerts homeostatic and pathogenic bioactivities ( 106 ). Elevated levels of TNF-α are observed in serum and hepatocytes of patients with acute or chronic hepatitis B ( 107 ), possibly through ERKs and NF-κB pathway ( 108 ). TNF-α may play a role in downregulating HBV replication in hepatocytes by non-cytopathic mechanisms and synergizing with IFN in suppressing viral replication ( 109 , 110 ).…”

Section: Role Of Cytokines Chemokines and Mirnas In Negative Regulation Of Ifn-α Therapy In Chb Infectionmentioning

confidence: 99%

Suppression of Interferon-α Treatment Response by Host Negative Factors in Hepatitis B Virus Infection

Wang

Tang

2021

Front. Med.

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Chronic hepatitis B virus (CHB) infection remains a major global public health issue for which there is still lacking effective curative treatment. Interferon-α (IFN-α) and its pegylated form have been approved as an anti-HBV drug with the advantage of antiviral activity and host immunity against HBV infection enhancement, however, IFN-α treatment failure in CHB patients is a challenging obstacle with 70% of CHB patients respond poorly to exogenous IFN-α treatment. The IFN-α treatment response is negatively regulated by both viral and host factors, and the role of viral factors has been extensively illustrated, while much less attention has been paid to host negative factors. Here, we summarized evidence of host negative regulators and parameters involved in IFN-α therapy failure, review the mechanisms responsible for these effects, and discuss the possible improvement of IFN-based therapy and the rationale of combining the inhibitors of negative regulators in achieving an HBV cure.

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Hepatitis B virus X protein up-regulates tumor necrosis factor-α expression in cultured mesangial cells via ERKs and NF-κB pathways

Cited by 10 publications

References 26 publications

Hepatitis�B virus X protein decreases nephrin expression and induces podocyte apoptosis via activating STAT3

Hepatitis�B virus X protein decreases nephrin expression and induces podocyte apoptosis via activating STAT3

Significance of mutations in hepatitis B virus X gene for the pathogenesis of HB-associated glomerulonephritis

Suppression of Interferon-α Treatment Response by Host Negative Factors in Hepatitis B Virus Infection

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