Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Surgery. 2020 Mar;167(3):560-568. doi: 10.1016/j.surg.2019.10.013. Epub 2019 Nov 21.
Glypican-3 plays a vital role in regulating embryonic morphogenesis of the liver. This study aimed to investigate associations of hepatic expressions of glypican-3 and alpha-smooth muscle actin with clinical parameters in biliary atresia.
Liver specimens were obtained from 20 biliary atresia infants and 7 non-biliary atresia controls. Relative mRNA expressions of glypican-3, alpha-smooth muscle actin, and signaling molecules of Wnt/β-catenin were measured using real-time polymerase chain reaction. Protein expressions of glypican-3 and alpha-smooth muscle actin were examined using immunohistochemistry. Masson's trichrome staining was conducted to evaluate the stage of liver fibrosis.
Up-regulation of glypican-3 mRNA expression was observed in biliary atresia livers, and its expression was positively associated with alpha-smooth muscle actin, β-catenin, c-Myc, and cyclin D-1. Immunostaining scores of glypican-3 and alpha-smooth muscle actin were significantly increased in biliary atresia livers. Biliary atresia patients with poor outcomes had significantly greater glypican-3 expression than those with good outcomes, consistent with hepatic alpha-smooth muscle actin expression analysis. Hepatic glypican-3 expression was associated with age, albumin, aspartate transaminase, and alkaline phosphatase in biliary atresia patients, while hepatic alpha-smooth muscle actin expression was correlated with alkaline phosphatase in the patients. Moreover, glypican-3 and alpha-smooth muscle actin expressions were positively associated with fibrosis stage in biliary atresia livers. There was a positive relationship between glypican-3 and alpha-smooth muscle actin expression in biliary atresia livers. Combined high expressions of glypican-3 and alpha-smooth muscle actin were associated with poor survival.
Hepatic overexpressions of glypican-3 and alpha-smooth muscle actin were associated with hepatic dysfunction and the degree of liver fibrosis in biliary atresia.
Glypican-3 在调节肝脏胚胎形态发生中起着至关重要的作用。本研究旨在探讨胆道闭锁患者肝脏中 Glypican-3 和α-平滑肌肌动蛋白的表达与临床参数的关系。
从 20 例胆道闭锁婴儿和 7 例非胆道闭锁对照中获得肝组织标本。采用实时聚合酶链反应测定 Glypican-3、α-平滑肌肌动蛋白和 Wnt/β-catenin 信号分子的相对 mRNA 表达。采用免疫组织化学法检测 Glypican-3 和α-平滑肌肌动蛋白的蛋白表达。采用 Masson 三色染色法评估肝纤维化分期。
胆道闭锁肝脏中观察到 Glypican-3 mRNA 表达上调，其表达与α-平滑肌肌动蛋白、β-catenin、c-Myc 和 cyclin D-1 呈正相关。胆道闭锁肝脏中 Glypican-3 和α-平滑肌肌动蛋白的免疫染色评分显著增加。预后不良的胆道闭锁患者的 Glypican-3 表达明显高于预后良好的患者，与肝α-平滑肌肌动蛋白表达分析一致。胆道闭锁患者的肝 Glypican-3 表达与年龄、白蛋白、天冬氨酸转氨酶和碱性磷酸酶有关，而肝α-平滑肌肌动蛋白表达与碱性磷酸酶有关。此外，Glypican-3 和α-平滑肌肌动蛋白在胆道闭锁肝脏中的表达与纤维化分期呈正相关。胆道闭锁肝脏中 Glypican-3 和α-平滑肌肌动蛋白的表达呈正相关。Glypican-3 和α-平滑肌肌动蛋白的联合高表达与生存不良有关。
胆道闭锁患者肝脏中 Glypican-3 和α-平滑肌肌动蛋白的过度表达与肝功能障碍和肝纤维化程度有关。
