The TMEM16A chloride channel as an alternative therapeutic target in cystic fibrosis.
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.
U.O.C. Genetica Medica, Istituto Giannina Gaslini, 16147 Genova, Italy.
Elvira
E
Sondo
U.O.C. Genetica Medica, Istituto Giannina Gaslini, 16147 Genova, Italy.
Emanuela
E
Caci
U.O.C. Genetica Medica, Istituto Giannina Gaslini, 16147 Genova, Italy. Electronic address: galietta@unige.it.
Luis J V
LJ
Galietta
D000818:Animals; D000075369:Anoctamin-1; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism
C476213:ANO1 protein, human; D000075369:Anoctamin-1; D018118:Chloride Channels; D009363:Neoplasm Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator
Airway epithelium; Chloride secretion; Cystic fibrosis; Goblet cell; Mucociliary clearance