Department of Nephrology, Shanghai Jiaotong University Affiliated Shanghai First People's Hospital, 100 Haining Road, Shanghai, 200080, China.
Arch Virol. 2013 Dec;158(12):2479-85. doi: 10.1007/s00705-013-1759-7. Epub 2013 Jun 21.
The hepatitis B virus X protein (HBx) is the most important determinant in viral pathogenesis. HBx regulates HBV replication, cellular transcription, signal transduction, proteasome activity and cell cycle progression. In this study, HK-2 cells were transiently transfected with the HBx gene using a eukaryotic vector, pcDNA3.1/myc-HBx. Transfection with the HBx gene increased the number of apoptotic cells. In addition, cultured HK-2 cells became irregular in shape. The expression of α-SMA and E-cadherin, TLR4, MHC-II and CD40 was increased. The transfection resulted in increased IL-1, IL-6, TNF-α and IFN-γ levels in the supernatant and decreased IL-4 in the supernatant. In conclusion, overexpression of the HBx gene in renal tubular epithelial cells induces apoptosis of HK-2 cells and promotes epithelial-mesenchymal transdifferentiation. HBx transfection upregulates the expression of immune molecules in renal tubular epithelial cells and induces an imbalance in cytokine levels.
乙型肝炎病毒 X 蛋白 (HBx) 是病毒发病机制中的最重要决定因素。HBx 调节 HBV 复制、细胞转录、信号转导、蛋白酶体活性和细胞周期进程。在这项研究中,使用真核载体 pcDNA3.1/myc-HBx 将 HBx 基因瞬时转染至 HK-2 细胞。HBx 基因的转染增加了凋亡细胞的数量。此外,培养的 HK-2 细胞形状变得不规则。α-SMA 和 E-钙黏蛋白、TLR4、MHC-II 和 CD40 的表达增加。转染导致上清液中 IL-1、IL-6、TNF-α 和 IFN-γ 水平升高,上清液中 IL-4 水平降低。总之,HBx 基因在肾小管上皮细胞中的过表达诱导 HK-2 细胞凋亡,并促进上皮-间充质转化。HBx 转染上调肾小管上皮细胞中免疫分子的表达,并诱导细胞因子水平失衡。