RT Journal Article
SR Electronic
T1 TMEM16A chloride channel does not drive mucus production
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201900462
DO 10.26508/lsa.201900462
VO 2
IS 6
A1 Simões, Filipa B
A1 Quaresma, Margarida C
A1 Clarke, Luka A
A1 Silva, Iris AL
A1 Pankonien, Ines
A1 Railean, Violeta
A1 Kmit, Arthur
A1 Amaral, Margarida D
YR 2019
UL http://www.life-science-alliance.org/content/2/6/e201900462.abstract
AB Airway mucus obstruction is the main cause of morbidity in cystic fibrosis, a disease caused by mutations in the CFTR Cl− channel. Activation of non-CFTR Cl− channels such as TMEM16A can likely compensate for defective CFTR. However, TMEM16A was recently described as a key driver in mucus production/secretion. Here, we have examined whether indeed there is a causal relationship between TMEM16A and MUC5AC production, the main component of respiratory mucus. Our data show that TMEM16A and MUC5AC are inversely correlated during differentiation of human airway cells. Furthermore, we show for the first time that the IL-4–induced TMEM16A up-regulation is proliferation-dependent, which is supported by the correlation found between TMEM16A and Ki-67 proliferation marker during wound healing. Consistently, the notch signaling activator DLL4 increases MUC5AC levels without inducing changes neither in TMEM16A nor in Ki-67 expression. Moreover, TMEM16A inhibition decreased airway surface liquid height. Altogether, our findings demonstrate that up-regulation of TMEM16A and MUC5AC is only circumstantial under cell proliferation, but with no causal relationship between them. Thus, although essential for airway hydration, TMEM16A is not required for MUC5AC production.