Ding Zequan, Zhang Ruyi, Zhu Wei, Lu Yao, Zhu Zhongxian, Xie Hua, Tang Weibing
Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, 72 Guangzhou Road, Nanjing 210000, Jiangsu Province, China.
Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, 72 Guangzhou Road, Nanjing 210000, Jiangsu Province, China.
Dig Liver Dis. 2025 Feb;57(2):385-393. doi: 10.1016/j.dld.2024.07.004. Epub 2024 Jul 22.
Liver fibrosis is a pathological feature of biliary atresia (BA). However, both histological fibrosis stage and existing biomarkers fail to predict prognosis at the time of hepatoportonterostomy (HPE).
To explore the role of collagen triple- helix repeat containing-1 (CTHRC1) in BA.
CTHRC1 expression levels were detected and its association with liver fibrosis stage was analyzed in patients with BA. Immunohistochemistry and immunofluorescent analyses were performed to detect the expression and localization of CTHRC1. Epithelial-mesenchymal transition (EMT) and proliferation were analyzed in cholangiocytes treated with recombinant human CTHRC1 protein. Survival analyses were performed to assess the prognostic value of CTHRC1 in patients with BA.
CTHRC1 was upregulated in BA, and its expression level was positively correlated with fibrosis-related markers and the severity of liver fibrosis. In liver tissue CTHRC1 was co-localized with CK19 and highly expressed in patients with severe liver fibrosis. Further experiments revealed that CTHRC1 promoted cholangiocyte EMT and proliferation. Additionally, CTHRC1 expression levels at HPE could predict the 2-year native liver survival (NLS).
CTHRC1 promotes the EMT and proliferation of cholangiocytes and indicate the stage of liver fibrosis. The CTHRC1 expression levels can predict outcomes of BA.
肝纤维化是胆道闭锁(BA)的一种病理特征。然而,组织学纤维化分期和现有的生物标志物均无法在肝门空肠吻合术(HPE)时预测预后。
探讨含胶原三螺旋重复序列-1(CTHRC1)在BA中的作用。
检测BA患者CTHRC1表达水平,并分析其与肝纤维化分期的相关性。采用免疫组织化学和免疫荧光分析检测CTHRC1的表达和定位。用重组人CTHRC1蛋白处理胆管细胞,分析上皮-间质转化(EMT)和增殖情况。进行生存分析以评估CTHRC1在BA患者中的预后价值。
CTHRC1在BA中上调,其表达水平与纤维化相关标志物及肝纤维化严重程度呈正相关。在肝组织中,CTHRC1与细胞角蛋白19(CK19)共定位,在严重肝纤维化患者中高表达。进一步实验表明,CTHRC1促进胆管细胞EMT和增殖。此外,HPE时CTHRC1表达水平可预测2年自体肝存活率(NLS)。
CTHRC1促进胆管细胞EMT和增殖,并提示肝纤维化阶段。CTHRC1表达水平可预测BA的预后。