Yang Y, Raper S E, Cohn J A, Engelhardt J F, Wilson J M
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor 48109.
Proc Natl Acad Sci U S A. 1993 May 15;90(10):4601-5. doi: 10.1073/pnas.90.10.4601.
Cystic fibrosis (CF) is an inherited disease of epithelial cell ion transport that is associated with pathology in multiple organ systems, including lung, pancreas, and liver. As treatment of the pulmonary manifestations of CF has improved, management of CF liver disease has become increasingly important in adult patients. This report describes an approach for treating CF liver disease by somatic gene transfer. In situ hybridization and immunocytochemistry analysis of rat liver sections indicated that the endogenous CFTR (cystic fibrosis transmembrane conductance regulator) gene is primarily expressed in the intrahepatic biliary epithelial cells. To specifically target recombinant genes to the biliary epithelium in vivo, recombinant adenoviruses expressing lacZ or human CFTR were infused retrograde into the biliary tract through the common bile duct. Conditions were established for achieving recombinant gene expression in virtually all cells of the intrahepatic bile ducts in vivo. Expression persisted in the smaller bile ducts for the duration of the experiment, which was 21 days. These studies suggest that it may be feasible to prevent CF liver disease by genetically reconstituting CFTR expression in the biliary tract, using an approach that is clinically feasible.
囊性纤维化（CF）是一种上皮细胞离子转运的遗传性疾病，与包括肺、胰腺和肝脏在内的多个器官系统的病理状况相关。随着CF肺部表现治疗方法的改进，CF肝病的管理在成年患者中变得越来越重要。本报告描述了一种通过体细胞基因转移治疗CF肝病的方法。对大鼠肝脏切片进行原位杂交和免疫细胞化学分析表明，内源性CFTR（囊性纤维化跨膜传导调节因子）基因主要在肝内胆管上皮细胞中表达。为了在体内将重组基因特异性靶向胆管上皮，将表达lacZ或人CFTR的重组腺病毒通过胆总管逆行注入胆道。建立了在体内几乎所有肝内胆管细胞中实现重组基因表达的条件。在为期21天的实验期间，较小胆管中的表达持续存在。这些研究表明，使用一种临床可行的方法，通过在胆道中基因重组CFTR表达来预防CF肝病可能是可行的。
