Hepatitis B virus X protein promotes renal epithelial-mesenchymal transition in human renal proximal tubule epithelial cells through the activation of NF-κB.

Abstract

HepatitisB virus(HBV)-associated glomerulo-nephritis is the most common extra-hepatic disorder occurring with hepatitisB virus infection. In the present study, we hypothesized that HBVXprotein(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, collagenI 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, phosphoinositide3-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.