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NATURE:小分子离子通道增加囊性纤维化气道上皮细胞的宿主防御

2019-03-16 海北 MedSci原创

最近,研究人员发现,顶端添加两性霉素B,一种形成非选择性离子通道的小分子,可以恢复HCO3-分泌,并增加来自囊性纤维化患者的气道上皮细胞的气道表面液体pH。

囊性纤维化跨膜传导调节因子(CFTR)中的功能丧失突变损害上皮HCO3-和Cl-分泌,降低气道表面液体pH,并损害囊性纤维化患者的呼吸道宿主防御。

最近,研究人员发现,顶端添加两性霉素B,一种形成非选择性离子通道的小分子,可以恢复HCO3-分泌,并增加来自囊性纤维化患者的气道上皮细胞的气道表面液体pH。

这些效应需要基底外侧Na +,K + -ATP酶,表明顶端两性霉素B通道在功能上与阴离子分泌的驱动剂相互作用。

两性霉素B还恢复了由不同突变导致的囊性纤维化患者气道上皮细胞的原代培养液中的气道表面液体pH,粘度和抗菌活性,包括不产生CFTR的患者。两性霉素B还可以在体帮助CFTR无效猪中气道表面液体pH的增加。

因此,非选择性小分子离子通道可以通过独立于CFTR的机制恢复囊性纤维化气道上皮细胞中的宿主防御,不依赖于基因型。


原始出处:

Muraglia KA et al. Small-molecule ion channels increase host defences in cystic fibrosis airway epithelia. NATURE, 2019; doi: 10.1038/s41586-019-1018-5.


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    2019-10-02 宋威
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    2019-12-12 wolongzxh
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    2019-06-17 liye789132251
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    2019-03-18 wincls
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