Roles of cell-cell adhesion molecules and apoptpsis effectors in the pathogenesis and disease processes of biliary atresia. Gene profiling assay using cDNA microarray

胆汁闭锁（BA）是导致婴儿肝纤维化的胆汁淤积最常见的原因之一。虽然BA的病因尚不清楚，但胆管板畸形、免疫介导的胆管损伤和/或细胞-细胞粘连，可能与细胞周期和细胞凋亡有关，已被认为在本病的发展中起重要作用。为了详细了解BA发病机制和疾病过程背后的遗传参与，我们使用Atlas人类cDNA表达阵列（Clonetech）评估了来自6名BA婴儿和2个对照组（正常肝脏和胆总管囊肿）的肝脏活检样本的原位基因表达谱。在4881个基因中，发现134个基因在几乎所有BA肝组织中过表达至少3倍，而25个基因被发现下调。编码细胞粘附分子、凋亡效应因子、细胞外基质、离子转运蛋白、免疫系统蛋白、细胞因子、生长因子、转录因子和代谢酶的基因在我们的研究中存在差异表达。本研究中观察到的基因表达变化可能与BA的发病机制有关，进而可能导致胆汁淤积、炎症和纤维化等继发性疾病过程。

Biliary atresia (BA) is one of the most common causes of cholestasis leading to hepatic fibrosis in infancy. Although the etiology of BA remains largely unknown, both ductal plate malformation, immune-mediated bile duct injury and/or cell-cell adhesion, possibly associated with cell cycle and apoptosis, have been suggested to play important roles in the development of this disease. To provide a detailed insight into the genetic involvement behind the pathogenesis and disease process of BA, we evaluated the in situ gene expression profile of liver biopsy samples obtained from six infants wlth BA and two controls (normal liver and choledochal cyst) using Atlas human cDNA expression arrays (Clonetech). Among the 4,881 genes present on the array, 134 genes were found to be overe-xpressed at least 3-fold in almost all liver tissues from BA compared to corresponding controls, whereas, 25 genes were found to be down-regulated. Genes encoding cell-cell adhesion molecules, apoptotic effectors, extracellular matrices, ion transporters, immune system proteins, cytokines, growth factors, transcription factors and metabolic enzymes were differentially expressed in our study. The changes in gene expression observed in this study may be associated with the pathogenesis of BA, which may in turn contribute to secondary disease processes such as cholestasis, inflammation and fibrosis.