Abnormal activation of OPN inflammation pathway in livers of children with biliary atresia and relationship to hepatic fibrosis

Objective: Aim of the Study was to investigate the expression of OPN (osteopontin) and its upper-downstream regulating factors in the biliary atretic liver and explore the relationship to progressive intrahepatic fibro-inflammation. Method: OPN expression in the livers of 18 children with biliary atresia (BA), 15 children with congenital biliary dilatation (CBD) and 8 normal controls were examined by immunostaining. Masson's trichrome stain was used to evaluate the level of hepatic fibrosis in each group. Western blotting and RT-polymerase chain reaction were respectively used to semiquantitatively analyze the NF-kappa B (nuclear factor-kappa B) and the TGF-beta 1mRNA (transforming growth factor-beta 1) expression in each group. Results: OPN expression was found in the epithelial cells of the intrahepatic bile duct in the BA group, and its intensity was 0,33 +/- 0.10, while there was only little expression of OPN in the epithelial cells of the intrahepatic bile ducts in the CBD) group and normal controls. There was a positive correlation between the intensity of OPN and the level of hepatic fibrosis in BA livers (r = 0.97). The intensity of NF-kappa B expression in BA livers (0.76 +/- 0.07) was much higher than that in CBD livers (0.25 +/- 0.04) or the livers of normal controls (0.22 +/- 0.02). A positive correlation was detected between the intensity of NF-kappa B and OPN in BA livers (r = 0.94). The expression of TGF-beta 1 mRNA in BA livers (1.46 +/- 0.17) was much higher than that in CBD livers (0.68 +/- 0.11). Little expression of TGF-beta 1 mRNA was detected in the livers of normal controls. A positive correlation was detected between the expression of TGF-beta 1 mRNA and the intensity of OPN in BA livers (r = 0.88). Conclusion: The abnormal activation of the OPN inflammation pathway might play a key role in the generation of intrallepatic fibrosis in BA. This progressive fibro-inflammation might be controlled by OPN and its upper-downstream regulating factors NF-kappa B and TGF-beta 1.