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. 2019 May;17(5):4223-4229.
doi: 10.3892/etm.2019.7453. Epub 2019 Mar 29.

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

Xiao-Yan Lei  1 , Xing-Xing Chen  1 , Yong-Hong Sun  1 , Ming-Dong Gao  1 , Xiao-Xia Hu  1 , Yan-Hong Suo  1
Affiliations

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

Xiao-Yan Lei et al. Exp Ther Med. 2019 May.

Abstract

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.

Keywords: apoptosis; hepatitis B virus X protein; nephrin; podocyte; signal transducer and activator of transcription 3.

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Figures

Figure 1.
Figure 1.
Western blot analysis of HBx protein expression in MPC5 cells following transfection with pEX-HBx. (A) HBx protein expression after transfection for 12–72 h; (B) HBx expression in different groups after transfection for 48 h. HBx, hepatitis B virus X protein.
Figure 2.
Figure 2.
Effects of HBx on the expression of nephrin protein. Values are presented as the mean ± standard deviation (n=3). (A) Western blot gel; (B) graphical representation of the results. **P<0.01. HBx, hepatitis B virus X protein.
Figure 3.
Figure 3.
Podocyte viability rate comparison between the groups. Values are presented as the mean ± standard deviation (n=3). **P<0.01. HBx, hepatitis B virus X protein.
Figure 4.
Figure 4.
Apoptotic rates of podocytes with or without HBx transfection. Values are presented as the mean ± standard deviation (n=3). (A) Flow cytometry results; (B) graphical representation of the results. **P<0.01. HBx, hepatitis B virus X protein. HBx, hepatitis B virus X protein; FITC, fluorescein isothiocyanate; PI, propidium iodide.
Figure 5.
Figure 5.
Effects of HBx on the protein levels of STAT3 and p-STAT3. Values are presented as the mean ± standard deviation (n=3). (A) Western blot gel; (B) graphical representation of the results. **P<0.01. HBx, hepatitis B virus X protein; STAT3, signal transducer and activator of transcription 3; p-, phosphorylation.
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