title: Abnormal activation of OPN inflammation pathway in livers of children with biliary atresia and relationship to hepatic fibrosis.
abstract: 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.
  
  
  METHODS
  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-kappaB (nuclear factor-kappaB) and the TGF-beta1mRNA (transforming growth factor-beta1) 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-kappaB 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-kappaB and OPN in BA livers (r = 0.94). The expression of TGF-beta1mRNA in BA livers (1.46 +/- 0.17) was much higher than that in CBD livers (0.68 +/- 0.11). Little expression of TGF-beta1mRNA was detected in the livers of normal controls. A positive correlation was detected between the expression of TGF-beta1mRNA and the intensity of OPN in BA livers (r = 0.88).
  
  
  CONCLUSIONS
  The abnormal activation of the OPN inflammation pathway might play a key role in the generation of intrahepatic fibrosis in BA. This progressive fibro-inflammation might be controlled by OPN and its upper-downstream regulating factors NF-kappaB and TGF-beta1.
authors.affiliation: Department of Pediatric Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: L
authors.initials: L
authors.lastname: Huang
authors.forename: M-F
authors.initials: MF
authors.lastname: Wei
authors.forename: J-X
authors.initials: JX
authors.lastname: Feng
mesh_terms: D001653:Bile Ducts, Intrahepatic / Q000378:metabolism; D001656:Biliary Atresia / Q000378:metabolism*; D002648:Child; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008099:Liver / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D053495:Osteopontin / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D053773:Transforming Growth Factor beta1; D053495:Osteopontin