Department of Otolaryngology-Head and Neck Surgery, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Laryngoscope. 2012 Sep;122(9):1898-905. doi: 10.1002/lary.23392. Epub 2012 Jun 18.
OBJECTIVES/HYPOTHESIS: Chronic sinusitis is nearly universal in humans with cystic fibrosis (CF) and is accompanied by sinus hypoplasia (small sinuses). However, whether impaired sinus development is a primary feature of loss of the cystic fibrosis transmembrane conductance regulator (CFTR) or a secondary consequence of chronic infection remains unknown. Our objective was to study the early pathogenesis of sinus disease in CF.
Animal/basic science research.
Sinus development was studied in a porcine CF model.
Porcine sinus epithelia expressed CFTR and exhibited transepithelial anion transport. Disruption of the CFTR gene eliminated both. Sinuses of newborn CF pigs were not infected and showed no evidence of inflammation, yet were hypoplastic at birth. Older CF pigs spontaneously developed sinus disease similar to that seen in humans with CF.
These results define a role for CFTR in sinus development and suggest the potential of the CF pig as a genetic model of CF-sinus disease in which to test therapeutic strategies to minimize sinus-related CF morbidity.
目的/假设：囊性纤维化（CF）患者的慢性鼻窦炎几乎普遍存在，且伴有鼻窦发育不全（鼻窦较小）。然而，鼻窦发育不良是否是囊性纤维化跨膜电导调节因子（CFTR）缺失的主要特征，还是慢性感染的次要后果，目前仍不清楚。我们的目的是研究 CF 中鼻窦疾病的早期发病机制。
动物/基础科学研究。
在猪 CF 模型中研究鼻窦发育情况。
猪鼻窦上皮细胞表达 CFTR，并表现出跨上皮阴离子转运。CFTR 基因的破坏消除了这两者。新生 CF 猪的鼻窦未被感染，也没有炎症迹象，但在出生时就发育不全。年龄较大的 CF 猪会自发地患上类似于 CF 患者的鼻窦疾病。
这些结果定义了 CFTR 在鼻窦发育中的作用，并表明 CF 猪可能成为 CF-鼻窦疾病的遗传模型，可用于测试治疗策略以最大程度地减少与鼻窦相关的 CF 发病率。
