Temporal regulation of CFTR expression during ovine lung development:: implications for CF gene therapy
Temporal regulation of CFTR expression during ovine lung development:: implications for CF gene therapy
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DOI：
10.1093/hmg/11.2.125
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发表时间：
2002-01-15
影响因子：
3.5
通讯作者：
Harris, A
中科院分区：
文献类型：
--
作者：
Broackes-Carter, FC;Mouchel, N;Harris, A
囊性纤维化跨膜电导调节蛋白 (CFTR) 是一种小电导氯离子通道，可能与包括上皮钠通道 (ENaC) 在内的其他通道直接相互作用。已知人类发育中期的气道上皮中的 CFTR 含量比出生后更为丰富。这可能是近期呼吸道上皮功能从氯化物分泌转变为钠吸收的变化的结果。或者，它可能反映了 CFTR 在气道上皮发育中的额外作用。尽管 CF 胎儿和婴儿的肺上皮很少表现出明显的组织学异常，但经常有炎症的证据。我们的目的是确定 CFTR 表达水平是否与羊胎肺的特定发育阶段或分化功能相关。我们通过妊娠期间 14 个时间点的 mRNA 定量分析来评估 CFTR 表达，结果在妊娠中期开始时显示出最高水平，随后逐渐下降直至足月。相反，ENaC 表达从妊娠晚期开始增加。这些结果支持 CFTR 在呼吸道上皮分化中的作用，并表明其表达水平不仅仅反映了临近足月时钠/氯总体流量的重大变化。这些观察结果可能对 CIF 基因治疗在出生后肺部的成功具有重要意义。
The cystic fibrosis transmembrane conductance regulator (CFTR) protein is a small conductance chloride ion channel that may interact directly with other channels including the epithelial sodium channel (ENaC). CFTR is known to be more abundant in the airway epithelium during the second trimester of human development than after birth. This could be a consequence of the change in function of the respiratory epithelium from chloride secretion to sodium absorption near term. Alternatively it might reflect an additional role for CFTR in the developing airway epithelium. Though the lung epithelia of CF fetuses and infants rarely show gross histological abnormalities, there is often evidence of inflammation. Our aim was to establish whether CFTR expression levels correlated with specific developmental stages or differentiated functions in the ovine fetal lung. We evaluated CFTR expression using a quantitative assay of mRNA at 14 time points through gestation and showed highest levels at the start of the second trimester followed by a gradual decline through to term. In contrast, ENaC expression increased from the start of the third trimester. These results support a role for CFTR in differentiation of the respiratory epithelium and suggest that its expression levels are not merely reflecting major changes in the sodium/chloride bulk flow close to term. These observations may have significant implications for the likely success of CIF gene therapy in the postnatal lung.