Expression and function of Anoctamin 1/TMEM16A calcium-activated chloride channels in airways of in vivo mouse models for cystic fibrosis research
| Autor: | Johanna J. Salomon, Dominik Leitz, Ina Lisewski, Pamela Millar-Büchner, Marcus A. Mall, Lisa Korsch, Katrin Schrimpf, Stephan Frings, Anne Hahn, Frank Möhrlen, Dennis Feigenbutz |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Epithelial sodium channel Male Cystic Fibrosis Physiology Clinical Biochemistry Cystic Fibrosis Transmembrane Conductance Regulator Bronchi Respiratory Mucosa Gene mutation Cystic fibrosis Epithelium ANO1 03 medical and health sciences Mice Chlorides Chloride Channels Physiology (medical) medicine Animals Secretion Epithelial Sodium Channels Anoctamin-1 Ion Transport biology Ussing chamber Chemistry Epithelial Cells respiratory system medicine.disease Cystic fibrosis transmembrane conductance regulator Cell biology Mice Inbred C57BL Trachea Disease Models Animal 030104 developmental biology biology.protein Respiratory epithelium Calcium Female Signal Transduction |
| Zdroj: | Pflugers Archiv : European journal of physiology. 470(9) |
| ISSN: | 1432-2013 |
| Popis: | Physiological processes of vital importance are often safeguarded by compensatory systems that substitute for primary processes in case these are damaged by gene mutation. Ca2+-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) Ca2+-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 Ca2+-dependent Cl- secretion, a CFTR deletion model (cftr-/-), and a CF pathology model that overexpresses the epithelial Na+ channel β-subunit (βENaC), 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 Ca2+-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 βENaC 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. |
| Databáze: | OpenAIRE |
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