Journal Article

A role for MHBs<sup>t167</sup>/HBx in hepatitis B virus-induced renal tubular cell apoptosis

Liu Hong, Jing Zhang, Jie Min, Jianrong Lu, Fanfan Li, Hang Li, Shuangping Guo and Qing Li

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 25, issue 7, pages 2125-2133
Published in print July 2010 | ISSN: 0931-0509
Published online January 2010 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfp737
A role for MHBst167/HBx in hepatitis B virus-induced renal tubular cell apoptosis

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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 κB (NF-κB) was activated in HBVGN renal tissues, especially in tubular cells. We therefore investigated the role of NF-κB in tubular epithelial cells with HBV infection.

Methods. Nuclear translocation of NF-κB and alpha subunit of NF-κB inhibitor (IκBα) phosphorylation were assessed by immunodetection following transfection of HK-2 cells with mhbst167 and/or hbx. Electrophoretic mobility shift assays (EMSA) and dual luciferase reporter assays (DLR) were used to further examine NF-κB activation following transfection. Hochest 33258 and NF-κB/terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) double staining were used to detect apoptosis and the correlation between NF-κB activation and apoptosis. Protein kinase C (PKC) assay and ERK phosphorylation were assayed for a possible mechanism of NF-κB activation.

Results. Cells transfected with mhbst167 and/or hbx increased NF-κB nuclear translocation, phosphor-IκBα, κB-DNA binding activity, κB-dependent transcription and apoptotic index compared to controls (P < 0.05). The nuclear distribution of NF-κB strongly correlated to cellular apoptosis. PKC activity and phosphor-ERK were also increased (P < 0.05) during the NF-κB activation process. However, all above parameters were diminished after pyrrolidine dithiocarbamate (PDTC)-incubation, a NF-κB inhibitor (P < 0.05).

Conclusion. MHBst167/HBx-induced NF-κB activation via the PKC/ERK pathway in renal tubular cells undergoing apoptosis may be involved in virally induced pathogenesis.

Keywords: apoptosis; HBx; MHBst167; NF-κB; renal tubular cells

Journal Article.  4886 words.  Illustrated.

Subjects: Nephrology

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