EXPRESSION OF THE CYSTIC-FIBROSIS GENE IN ADULT HUMAN LUNG
EXPRESSION OF THE CYSTIC-FIBROSIS GENE IN ADULT HUMAN LUNG
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DOI：
10.1172/jci117028
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发表时间：
1994-02-01
影响因子：
15.9
通讯作者：
WILSON, JM
中科院分区：
文献类型：
--
作者：
ENGELHARDT, JF;ZEPEDA, M;WILSON, JM
了解囊性纤维化（CF）中的肺部疾病和开发有效的基因治疗的关键是成人肺中CF基因表达的分布和调控的定义。先前的研究已经在人支气管粘膜下腺体中检测到CF基因的产物，CF跨膜传导调节因子（CFTR）。在这份报告中，我们的特点是CFTR RNA和蛋白质的分布在远端气道和肺泡的人肺。通过原位杂交和免疫细胞化学分析来自8个人肺的样品的CFTR表达。CFTR在远端肺的每个水平的上皮细胞亚群中检测到，包括近端、末端和呼吸性细支气管以及肺泡。然而，样品之间CFTR表达水平存在实质性变化。在细支气管中，CFTR蛋白定位于顶端质膜，主要存在于无纤毛细胞亚群中。CFTR在近端细支气管中以与Clara细胞标记物CC10相同的分布表达，然而，在未检测到CC10的更远端细支气管和肺泡中表达不一致。这些研究表明，远端肺的上皮细胞可能在CF的发病机制中发挥主要作用，并扩大了在基因治疗开发中应考虑的靶细胞谱。
Critical to an understanding of the pulmonary disease in cystic fibrosis (CF) and the development of effective gene therapies is a definition of the distribution and regulation of CF gene expression in adult human lung. Previous studies have detected the product of the CF gene, the CF transmembrane conductance regulator (CFTR), in submucosal glands of human bronchi. In this report, we have characterized the distribution of CFTR RNA and protein in the distal airway and alveoli of human lungs. Samples from eight human lungs were analyzed for CFTR expression by in situ hybridization and immunocytochemistry. CFTR was detected in a subpopulation of epithelial cells at every level of the distal lung, including proximal, terminal, and respiratory bronchioles, and the alveoli. However, there was substantial variation in the level of CFTR expression between samples. In bronchioles, CFTR protein localized to the apical plasma membrane and was found primarily in a subpopulation of nonciliated cells. CFTR was expressed in the same distribution as the Clara cell marker CC10 in proximal bronchioles, however, expression was discordant in the more distal bronchioles and alveoli where CC10 was not detected. These studies suggest that epithelial cells of the distal lung may play a primary role in the pathogenesis of CF as well as expand the spectrum of target cells that should be considered in the development of gene therapies.