Sasaki H, Nio M, Iwami D, Funaki N, Sano N, Ohi R, Sasano H
Department of Pathology, Tohoku University School of Medicine, Sendai, Japan.
Pathol Int. 2001 Dec;51(12):923-32. doi: 10.1046/j.1440-1827.2001.01304.x.
Biliary atresia (BA) is the most common cause of obstructive jaundice in infancy. Although the etiology of BA remains unknown, the ductal plate malformation has been considered to play an important role in the development of BA. Cell-cell adhesion has long been recognized as one of the most important processes in organogenesis. E-cadherin is involved in cell-cell adhesion, together with the catenins. Abnormalities of E-cadherin and associated catenins have not been examined in detail in the liver with BA. We therefore examined immunolocalization of E-cadherin and alpha- and beta-catenins in the BA liver (n = 45) and compared the findings with those in non-BA (n = 11) and fetal liver (n = 21). We semiquantitatively evaluated the findings using H score, which were generated according to the percentage of immunopositive cells and their immunointensity. We also examined mRNA localization of E-cadherin using mRNA in situ hybridization. We then studied the correlation of E-cadherin immunoreactivity with apoptotic cells, and cyclin-dependent kinase inhibitor p27Kip1 immunolocalization of bile duct cells in BA liver (n = 10) and fetal liver (n = 10). In fetal liver, H score of E-cadherin, but not of alpha- and beta-catenins, was significantly lower in the remodeling stage than in the ductal plate (P = 0.0034) and remodeled stages (P = 0.0024). In addition, the H score of E-cadherin, but not alpha- and beta-catenin, in bile duct cells was significantly lower in BA liver than in non-BA liver (P = 0.0132). E-cadherin mRNA hybridization signals were relatively conserved in bile duct cells of BA liver, but decreased in remodeling ductal plate cells of fetal liver. An inverse correlation was detected between the H score of E-cadherin and the TUNEL labeling index (LI) in both fetal and BA liver. In contrast, a positive correlation was detected between the H score of E-cadherin and p27 LI in both fetal and BA liver. These findings suggest that impaired expression of E-cadherin in bile ducts may play an important role in the biological features of BA, possibly associated with cell cycle and apoptosis.
胆道闭锁（BA）是婴儿期梗阻性黄疸最常见的病因。尽管BA的病因尚不清楚，但导管板畸形被认为在BA的发生发展中起重要作用。细胞间黏附长期以来一直被认为是器官发生中最重要的过程之一。E-钙黏蛋白与连环蛋白一起参与细胞间黏附。在BA肝脏中，尚未对E-钙黏蛋白及相关连环蛋白的异常进行详细研究。因此，我们检测了45例BA肝脏中E-钙黏蛋白、α-连环蛋白和β-连环蛋白的免疫定位，并将结果与11例非BA肝脏和21例胎儿肝脏的结果进行比较。我们使用H评分对结果进行半定量评估，H评分根据免疫阳性细胞的百分比及其免疫强度生成。我们还使用mRNA原位杂交检测了E-钙黏蛋白的mRNA定位。然后，我们研究了BA肝脏（n = 10）和胎儿肝脏（n = 10）中E-钙黏蛋白免疫反应性与凋亡细胞以及胆管细胞中细胞周期蛋白依赖性激酶抑制剂p27Kip1免疫定位之间的相关性。在胎儿肝脏中，重塑期E-钙黏蛋白的H评分显著低于导管板期（P = 0.0034）和重塑期（P = 0.0024），而α-连环蛋白和β-连环蛋白的H评分无显著差异。此外，BA肝脏胆管细胞中E-钙黏蛋白的H评分显著低于非BA肝脏（P = 0.0132），而α-连环蛋白和β-连环蛋白的H评分无显著差异。BA肝脏胆管细胞中E-钙黏蛋白mRNA杂交信号相对保守，但胎儿肝脏重塑导管板细胞中的信号减少。在胎儿肝脏和BA肝脏中，均检测到E-钙黏蛋白的H评分与TUNEL标记指数（LI）呈负相关。相反，在胎儿肝脏和BA肝脏中，均检测到E-钙黏蛋白的H评分与p27 LI呈正相关。这些发现表明，胆管中E-钙黏蛋白表达受损可能在BA的生物学特征中起重要作用，可能与细胞周期和凋亡有关。
