Physiological processes of vital importance are often safeguarded by compensatory systems that substitute for primary processes in case these are damaged by gene mutation. Ca(2+)-dependent Cl(-) secretion in airway epithelial cells may provide such a compensatory mechanism for impaired Cl(-) secretion via cystic fibrosis transmembrane conductance regulator (CFTR) channels in cystic fibrosis (CF). Anoctamin 1 (ANO1) Ca(2+)-gated Cl(-) channels are known to contribute to calcium-dependent Cl(-) secretion in tracheal and bronchial epithelia. In the present study, two mouse models of CF were examined to assess a potential protective function of Ca(2+)-dependent Cl(-) secretion, a CFTR deletion model (cftr(-/-)), and a CF pathology model that overexpresses the epithelial Na(+) channel beta-subunit (betaENaC), which is encoded by the Scnn1b gene, specifically in airway epithelia (Scnn1b-Tg). The expression levels of ANO1 were examined by mRNA and protein content, and the channel protein distribution between ciliated and non-ciliated epithelial cells was analyzed. Moreover, Ussing chamber experiments were conducted to compare Ca(2+)-dependent Cl(-) secretion between wild-type animals and the two mouse models. Our results demonstrate that CFTR and ANO1 channels were co-expressed with ENaC in non-ciliated cells of mouse tracheal and bronchial epithelia. Ciliated cells did not express these proteins. Despite co-localization of CFTR and ANO1 in the same cell type, cells in cftr(-/-) mice displayed no altered expression of ANO1. Similarly, ANO1 expression was unaffected by betaENaC overexpression in the Scnn1b-Tg line. These results suggest that the CF-related environment in the two mouse models did not induce ANO1 overexpression as a compensatory system.
- Hahn, A.
- Salomon, J. J.
- Leitz, D.
- Feigenbutz, D.
- Korsch, L.
- Lisewski, I.
- Schrimpf, K.
- Millar-Buchner, P.
- Mall, M. A.
- Frings, S.
- Mohrlen, F.
Keywords
- Airway epithelium
- Anoctamin
- Chloride secretion
- Cystic fibrosis
- Mouse models
- Tmem16a
