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  • Title: A role for MHBst167/HBx in hepatitis B virus-induced renal tubular cell apoptosis.
    Author: Hong L, Zhang J, Min J, Lu J, Li F, Li H, Guo S, Li Q.
    Journal: Nephrol Dial Transplant; 2010 Jul; 25(7):2125-33. PubMed ID: 20118485.
    Abstract:
    BACKGROUND: The pathogenesis of hepatitis B virus (HBV)-associated glomerulonephritis (HBVGN) is generally believed to be immune complex deposition. However, the presence of HBV-DNA and -RNA in HBVGN renal tissues suggested a direct virally induced injury. We previously showed that nuclear factor kappaB (NF-kappaB) was activated in HBVGN renal tissues, especially in tubular cells. We therefore investigated the role of NF-kappaB in tubular epithelial cells with HBV infection. METHODS: Nuclear translocation of NF-kappaB and alpha subunit of NF-kappaB inhibitor (IkappaBalpha) phosphorylation were assessed by immunodetection following transfection of HK-2 cells with mhbs(t167) and/or hbx. Electrophoretic mobility shift assays (EMSA) and dual luciferase reporter assays (DLR) were used to further examine NF-kappaB activation following transfection. Hochest 33258 and NF-kappaB/terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) double staining were used to detect apoptosis and the correlation between NF-kappaB activation and apoptosis. Protein kinase C (PKC) assay and ERK phosphorylation were assayed for a possible mechanism of NF-kappaB activation. RESULTS: Cells transfected with mhbs(t167) and/or hbx increased NF-kappaB nuclear translocation, phosphor-IkappaBalpha, kappaB-DNA binding activity, kappaB-dependent transcription and apoptotic index compared to controls (P < 0.05). The nuclear distribution of NF-kappaB strongly correlated to cellular apoptosis. PKC activity and phosphor-ERK were also increased (P < 0.05) during the NF-kappaB activation process. However, all above parameters were diminished after pyrrolidine dithiocarbamate (PDTC)-incubation, a NF-kappaB inhibitor (P < 0.05). CONCLUSION: MHBs(t167)/HBx-induced NF-kappaB activation via the PKC/ERK pathway in renal tubular cells undergoing apoptosis may be involved in virally induced pathogenesis.
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