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.


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.
Huang
L
L
Department of Pediatric Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
Wei
M-F
MF
Feng
J-X
JX
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
D016328:NF-kappa B; D053773:Transforming Growth Factor beta1; D053495:Osteopontin