Huang L, Wei M-F, Feng J-X
Department of Pediatric Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
Eur J Pediatr Surg. 2008 Aug;18(4):224-9. doi: 10.1055/s-2008-1038483. Epub 2008 Aug 14.
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.
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.
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).
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.
本研究旨在探讨骨桥蛋白（OPN）及其上下游调控因子在胆道闭锁肝脏中的表达情况，并探究其与进行性肝内纤维炎症的关系。
采用免疫染色法检测18例胆道闭锁（BA）患儿、15例先天性胆管扩张症（CBD）患儿及8例正常对照儿童肝脏中OPN的表达。采用Masson三色染色法评估各组肝纤维化程度。分别采用蛋白质免疫印迹法和逆转录聚合酶链反应半定量分析各组中核因子κB（NF-κB）和转化生长因子β1mRNA（TGF-β1mRNA）的表达。
BA组肝内胆管上皮细胞中有OPN表达，其强度为0.33±0.10，而CBD组和正常对照儿童肝内胆管上皮细胞中OPN仅少量表达。BA肝脏中OPN强度与肝纤维化程度呈正相关（r = 0.97）。BA肝脏中NF-κB表达强度（0.76±0.07）明显高于CBD肝脏（0.25±0.04）或正常对照肝脏（0.22±0.02）。BA肝脏中NF-κB强度与OPN呈正相关（r = 0.94）。BA肝脏中TGF-β1mRNA表达（1.46±0.17）明显高于CBD肝脏（0.68±0.11）。正常对照肝脏中未检测到TGF-β1mRNA的表达。BA肝脏中TGF-β1mRNA表达与OPN强度呈正相关（r = 0.88）。
OPN炎症通路的异常激活可能在BA肝内纤维化的发生中起关键作用。这种进行性纤维炎症可能受OPN及其上下游调控因子NF-κB和TGF-β1的控制。
