Role of TGF-β1/p38 MAPK pathway in hepatitis B virus-induced tubular epithelial-myofibroblast transdifferentiation

Objective: This study is to investigate the hepatitis B virus (HBV)-induced tubular epithelial-myofibroblast transdifferentiation (TEMT) in human renal tubular epithelial HK-2 cells. Methods: Human proximal tubular epithelial HK-2 cells were cultured. These HK-2 cells were divided into 4 groups: the blank control group, the vector control group, the HBV-transfected group, and the inhibitor-treated group. Transfection was performed with lipofectamine. Measurements of hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) in culture supernatant were determined by electrochemiluminescence immunoassay. Immunocytochemical staining, reverse transcription PCR (RT-PCR), and Western blot analysis were performed to detect the mRNA and protein expression levels, respectively. Results: The immunocytochemical staining showed that, the expression level of E-cadherin was dramatically decreased, while the alpha-SMA expression level was significantly elevated, in HBV-transfected HK-2 cells. The mRNA level of TGF-beta 1 and the protein level of p-p38 mitogen-activated protein kinase (MAPK) were elevated in HK-2 cells transfected with HBV. When treated with the p38 MAPK-specific inhibitor, the activation of p38 MAPK was eliminated in HBV-transfected HK-2 cells. In addition, the altered expression levels of E-cadherin and alpha-SMA, the increased contents of HBeAg and HBsAg in the culture supernatant, as well as the morphological changes of TEMT in HBV-transfected HK-2 cells, were all reversed by the inhibiter treatment. Conclusion: HBV transfection could induce TEMT in HK-2 cells, which was mediated by the TGF-beta 1/p38 MAPK pathway. These findings provide new insights into the prevention and treatment of HBV-associated glomerulonephritis.