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.

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-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).

CONCLUSION:

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: L Huang, M-F Wei, J-X Feng
• Journal: European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift fur Kinderchirurgie (Eur J Pediatr Surg) Vol. 18 Issue 4 Pg. 224-9 (Aug 2008) ISSN: 0939-7248 [Print] United States
• PMID: 18704890 (Publication Type: Journal Article)

Chemical References

• NF-kappa B
• Transforming Growth Factor beta1
• Osteopontin

Topics

• Bile Ducts, Intrahepatic (metabolism)
• Biliary Atresia (metabolism)
• Child
• Disease Progression
• Humans
• Immunohistochemistry
• Infant
• Liver (metabolism)
• Liver Cirrhosis (metabolism)
• NF-kappa B (metabolism)
• Osteopontin (metabolism)
• Transforming Growth Factor beta1 (metabolism)