PT  - JOURNAL ARTICLE
AU  - Filipa B Simões
AU  - Margarida C Quaresma
AU  - Luka A Clarke
AU  - Iris AL Silva
AU  - Ines Pankonien
AU  - Violeta Railean
AU  - Arthur Kmit
AU  - Margarida D Amaral
TI  - TMEM16A chloride channel does not drive mucus production
AID  - 10.26508/lsa.201900462
DP  - 2019 Dec 01
TA  - Life Science Alliance
PG  - e201900462
VI  - 2
IP  - 6
4099  - https://www.life-science-alliance.org/content/2/6/e201900462.short
4100  - https://www.life-science-alliance.org/content/2/6/e201900462.full
SO  - Life Sci. Alliance2019 Dec 01; 2
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.