Sondo Elvira, Caci Emanuela, Galietta Luis J V
U.O.C. Genetica Medica, Istituto Giannina Gaslini, 16147 Genova, Italy.
U.O.C. Genetica Medica, Istituto Giannina Gaslini, 16147 Genova, Italy.
Int J Biochem Cell Biol. 2014 Jul;52:73-6. doi: 10.1016/j.biocel.2014.03.022. Epub 2014 Apr 1.
Cystic fibrosis (CF), a multiorgan genetic disease, is caused by loss of function of CFTR, a cAMP-regulated anion channel. In CF airway epithelia, defective Cl(-) and bicarbonate secretion impairs mucociliary clearance and other innate defense mechanisms, favoring the colonization of the lungs by highly virulent bacteria. The airway epithelium expresses TMEM16A, a second type of Cl(-) channel that is activated by cytosolic Ca(2+). TMEM16A is particularly expressed in goblet cells. This specific localization could be important in the release and hydration of mucins. Activation of TMEM16A with pharmacological agents could circumvent the primary defect in CF. This strategy needs to be carefully designed and tested to avoid possible undesired effects due to the expression of TMEM16A in other cell types such as bronchial smooth muscle cells. This article is part of a Directed Issue entitled: Cystic Fibrosis: From o-mics to cell biology, physiology, and therapeutic advances.
囊性纤维化（CF）是一种多器官遗传病，由CFTR（一种受环磷酸腺苷调节的阴离子通道）功能丧失引起。在CF气道上皮细胞中，氯离子（Cl⁻）和碳酸氢盐分泌缺陷会损害黏液纤毛清除功能及其他固有防御机制，有利于高毒力细菌在肺部定植。气道上皮细胞表达TMEM16A，这是另一种由胞质钙离子（Ca²⁺）激活的Cl⁻通道。TMEM16A在杯状细胞中特别表达。这种特定定位可能在黏蛋白的释放和水合作用中起重要作用。用药物激活TMEM16A可能会规避CF的原发性缺陷。该策略需要精心设计和测试，以避免由于TMEM16A在其他细胞类型（如支气管平滑肌细胞）中的表达而可能产生的不良影响。本文是名为“囊性纤维化：从组学到细胞生物学、生理学及治疗进展”的定向专题的一部分。
