Hepatitis B virus X protein promotes renal epithelial-mesenchymal transition in human renal proximal tubule epithelial cells through the activation of NF-κB.
Hepatitis B virus (HBV)-associated glomerulo-nephritis is the most common extra-hepatic disorder occurring with hepatitis B virus infection. In the present study, we hypothesized that HBV X protein (HBx) may play a critical role in renal interstitial fibrosis, as HBx has been shown to induce epithelial-mesenchymal transition (EMT) in renal cells. For this purpose, we successfully transfected HBx plasmid into human renal proximal tubule epithelial cells (HK-2 cells). We found that transfection with HBx plasmid significantly downregulated E-cadherin expression and upregulated α-smooth muscle actin, collagen I and fibronectin expression in a time- and concentration-dependent manner (at the lower concentrations and earlier time points). HBx also increased nuclear factor-κB (NF-κB) phosphorylation in a time- and concentration-dependent manner (again at the lower concentrations and earlier time points); however, it did not alter the phosphorylation of Smad2, Smad3, p38, phosphoinositide 3-kinase (PI3K) or extracellular signal-regulated kinase (ERK). Thus, the findings of this study demonstrate that HBx promotes EMT in renal HK-2 cells, and the potential underlying mechanisms may involve the activation of the NF-κB signaling pathway.
Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
Mei
M
Li
Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
Liping
L
Hu
Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
Fengxin
F
Zhu
Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
Zhangmei
Z
Zhou
Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
Jianwei
J
Tian
Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
Jun
J
Ai
D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051785:Smad Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D048049:Extracellular Signal-Regulated MAP Kinases; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D051785:Smad Proteins; D015534:Trans-Activators; D053773:Transforming Growth Factor beta1; D054334:Viral Regulatory and Accessory Proteins; D048051:p38 Mitogen-Activated Protein Kinases; C057628:hepatitis B virus X protein