Summary
Notch1 plays an important role in the regulation of immune responses and epithelial–mesenchymal transdifferentiation (EMT). Previous studies have observed inflammatory cell infiltration and tubulointerstitial fibrosis in the renal biopsies from patients with HBV‐associated glomerulonephritis (HBV‐GN). We hypothesized that Notch1 may be involved in the progression of HBV‐GN. In this study, we evaluated the distribution of Notch1 in patients with HBV‐GN. Our results showed that Notch1 was mainly distributed in renal tubules and the interstitial area, and the expression levels of Notch1 had a positive correlation with the renal tubular pathology. In this respect, we used human proximal tubular epithelial cells (HK‐2) as target cells, which were transiently transfected with the hepatitis B virus X (HBx) gene using a eukaryotic vector. HBx expression resulted in significantly increased detection of Notch1, alpha‐smooth muscle actin (α‐SMA), major histocompatibility complex‐II (MHC‐II), CD40 and interleukin‐4 (IL‐4). At the same time, E‐cadherin and interferon‐γ (IFN‐γ) expression levels were significantly inhibited. These HBx‐induced phenotypes were exacerbated by upregulation of Notch1. Knock‐down of Notch1 by specific shRNA caused decreases of α‐SMA, MHC‐II, CD40 and IL‐4, and increases of E‐cadherin and IFN‐γ. These findings suggest that Notch1 is significantly associated with renal tubular and interstitial lesions. Notch1 can mediate HBx‐induced EMT of HK‐2 cells, promote HBx‐induced increases in immune molecule expression and exacerbation of cytokine disorders, which may contribute to the progression of HBV‐GN. Inhibitors of Notch1 signalling may be useful as new therapeutics for the treatment of HBV‐GN.