Dupuit F, Kälin N, Brézillon S, Hinnrasky J, Tümmler B, Puchelle E
Institut National de la Santé et de la Recherche Médicale U. 314, Hôpital Maison Blanche, Reims, France.
J Clin Invest. 1995 Sep;96(3):1601-11. doi: 10.1172/JCI118199.
Human nasal polyps from non-CF and delta F 508 homozygous CF patients were used to compare the expression of CFTR and markers epithelial differentiation, such as cytokeratins (CK) and desmoplakins (DP), at the transcriptional and translational levels. mRNA expression was assessed by semiquantitative RT/PCR kinetic assays while the expression and distribution of proteins were evaluated by immunofluorescence analysis. In parallel, for each nasal tissue specimen, the importance of surface epithelium remodeling and inflammation was estimated after histological observations. Our results show that the steady-state levels of CFTR, CK13, CK18, CK18, CK14, or DP 1 mRNA transcripts in delta F 508 CF nasal polyps were not significantly different from those of non-CF tissues. A variability in the CFTR mRNA transcript level and in the pattern of CFTR immunolabeling has been observed between the different tissue samples. However, no relationship was found between the level of CFTR mRNA transcripts and the CFTR protein expression and distribution, either in the non-CF or in the CF group. The histological observations of non-CF and CF nasal polyp tissue indicated that the huge variations in the expression and distribution of the CFTR protein were associated with the variations in the degree of surface epithelium remodeling and inflammation in the lamina propria. A surface epithelium, showing a slight basal cell hyperplasia phenotype associated with diffuse inflammation, was mainly characterized by a CFTR protein distribution at the apex of ciliated cells in both non-CF and CF specimens. In contrast, in a remodeled surface epithelium associated with severe inflammation, CFTR protein presented either a diffuse distribution in the cytoplasm of ciliated cells, or was absent. These results suggest that abnormal expression and distribution of the CFTR protein of CF airways is not only caused by CFTR mutations. Airway surface epithelium remodeling and inflammation could play a critical role in the posttranscriptional and/or the posttranslational regulation of the CFTR protein expression in non-CF and CF airways.
来自非囊性纤维化（non-CF）患者和ΔF508纯合囊性纤维化（CF）患者的人鼻息肉被用于比较CFTR以及上皮分化标志物（如细胞角蛋白（CK）和桥粒斑蛋白（DP））在转录和翻译水平上的表达。通过半定量RT/PCR动力学分析评估mRNA表达，同时通过免疫荧光分析评估蛋白质的表达和分布。同时，对于每个鼻组织标本，在组织学观察后评估表面上皮重塑和炎症的重要性。我们的结果表明，ΔF508 CF鼻息肉中CFTR、CK13、CK18、CK18、CK14或DP 1 mRNA转录本的稳态水平与非CF组织中的水平无显著差异。在不同组织样本之间观察到CFTR mRNA转录本水平和CFTR免疫标记模式存在差异。然而，在非CF组或CF组中，均未发现CFTR mRNA转录本水平与CFTR蛋白表达及分布之间存在关联。非CF和CF鼻息肉组织的组织学观察表明，CFTR蛋白表达和分布的巨大差异与固有层表面上皮重塑程度和炎症程度的差异相关。在非CF和CF标本中，表面上皮呈现出与弥漫性炎症相关的轻微基底细胞增生表型，其主要特征是CFTR蛋白分布在纤毛细胞的顶端。相反，在与严重炎症相关的重塑表面上皮中，CFTR蛋白要么在纤毛细胞的细胞质中呈弥漫性分布，要么缺失。这些结果表明，CF气道中CFTR蛋白的异常表达和分布不仅是由CFTR突变引起的。气道表面上皮重塑和炎症可能在非CF和CF气道中CFTR蛋白表达的转录后和/或翻译后调节中起关键作用。
