Previous analysis of CFTR-knockout (CFTR−/−) in piglets has provided important insights into the pathology of cystic fibrosis. However, controversies exist as to the true contribution of CFTR to the pH balance in airways and intestine. We therefore compared ion transport properties in newborn wild-type (CFTR+/+) and CFTR-knockout (CFTR−/− piglets). Tracheas of CFTR−/− piglets demonstrated typical cartilage malformations and muscle cell bundles. CFTR−/− airway epithelial cells showed enhanced lipid peroxidation, suggesting inflammation early in life. CFTR was mainly expressed in airway submucosal glands and was absent in lungs of CFTR−/− piglets, while expression of TMEM16A was uncompromised. mRNA levels for TMEM16A, TMEM16F, and αβγENaC were unchanged in CFTR−/− airways, while mRNA for SLC26A9 appeared reduced. CFTR was undetectable in epithelial cells of CFTR−/− airways and intestine. Small intestinal epithelium of CFTR−/− piglets showed mucus accumulation. Secretion of both electrolytes and mucus was activated by stimulation with prostaglandin E2 and ATP in the intestine of CFTR+/+, but not of CFTR−/− animals. pH was measured inside small bronchi using a pH microelectrode and revealed no difference between CFTR+/+ and CFTR−/− piglets. Intracellular pH in porcine airway epithelial cells revealed only a small contribution of CFTR to bicarbonate secretion, which was absent in cells from CFTR−/− piglets. In contrast to earlier reports, our data suggest a minor impact of CFTR on ASL pH. In contrast, enhanced amiloride-sensitive Na⁺ absorption may contribute to lung pathology in CFTR−/− piglets, along with a compromised CFTR- and TMEM16A-dependent Cl⁻ transport.

仔猪中CFTR基因敲除（CFTR-/-）的先前分析为囊性纤维化的病理学提供了重要见解。然而，关于CFTR对气道和肠中pH平衡的真正贡献存在争议。因此，我们比较了新生儿野生型（CFTR + / +）和CFTR敲除（CFTR-/-仔猪）的离子迁移特性。CFTR-/-仔猪的气管表现出典型的软骨畸形和肌肉细胞束。CFTR-/-气道上皮细胞显示脂质过氧化作用增强，提示生命早期会发炎。CFTR主要在气道粘膜下腺中表达，而在CFTR-/-仔猪的肺中不存在，而TMEM16A的表达却毫不妥协。在CFTR-/-气道中，TMEM16A，TMEM16F和αβγENaC的mRNA水平没有变化，而SLC26A9的mRNA却降低了。在CFTR-/-气道和肠的上皮细胞中未检测到CFTR。CFTR-/-仔猪的小肠上皮显示出粘液积聚。电解质和粘液的分泌均通过CFTR + / +肠中的前列腺素E2和ATP刺激而被激活，但CFTR-/-动物则没有。使用pH微电极在小支气管内测量pH，发现CFTR + / +和CFTR-/-仔猪之间没有差异。猪气道上皮细胞的细胞内pH值显示CFTR对碳酸氢盐分泌的贡献很小，而CFTR-/-仔猪的细胞中没有。与早期的报告相比，我们的数据表明CFTR对ASL pH的影响较小。相反，增强的阿米洛利敏感钠 电解质和粘液的分泌均通过CFTR + / +肠中的前列腺素E2和ATP刺激而被激活，但CFTR-/-动物则没有。使用pH微电极在小支气管内测量pH，发现CFTR + / +和CFTR-/-仔猪之间没有差异。猪气道上皮细胞的细胞内pH值显示CFTR对碳酸氢盐分泌的贡献很小，而CFTR-/-仔猪的细胞中没有。与早期的报告相比，我们的数据表明CFTR对ASL pH的影响较小。相反，增强的阿米洛利敏感钠 电解质和粘液的分泌被CFTR + / +的肠中的前列腺素E2和ATP刺激而激活，但CFTR-/-的动物则没有。使用pH微电极在小支气管内测量pH，发现CFTR + / +和CFTR-/-仔猪之间没有差异。猪气道上皮细胞的细胞内pH值显示CFTR对碳酸氢盐分泌的贡献很小，而CFTR-/-仔猪的细胞中没有。与早期的报告相比，我们的数据表明CFTR对ASL pH的影响较小。相反，增强的阿米洛利敏感钠 猪气道上皮细胞的细胞内pH值显示CFTR对碳酸氢盐分泌的贡献很小，而CFTR-/-仔猪的细胞中没有。与早期的报告相比，我们的数据表明CFTR对ASL pH的影响较小。相反，增强的阿米洛利敏感钠 猪气道上皮细胞的细胞内pH值显示CFTR对碳酸氢盐分泌的贡献很小，而CFTR-/-仔猪的细胞中没有。与早期的报告相比，我们的数据表明CFTR对ASL pH的影响较小。相反，增强的阿米洛利敏感钠⁺吸收可以在CFTR有助于肺病理学- / -仔猪，具有受损CFTR-和TMEM16A依赖性氯沿^-运输。