Cabrita, Ines and Benedetto, Roberta and Wanitchakool, Podchanart and Lerias, Joana and Centeio, Raquel and Ousingsawat, Jiraporn and Schreiber, Rainer and Kunzelmann, Karl (2021) TMEM16A Mediates Mucus Production in Human Airway Epithelial Cells. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 64 (1). pp. 50-58. ISSN 1044-1549, 1535-4989
Full text not available from this repository. (Request a copy)Abstract
TMEM16A is a Ca2+-activated chloride channel that was shown to enhance production and secretion of mucus in inflamed airways. It is, however, not clear whether TMEM16A directly supports mucus production, or whether mucin and TMEM16A are upregulated independently during inflammatory airway diseases such as asthma and cystic fibrosis (CF). We examined this question using BCi-NS1 cells, a human airway basal cell line that maintains multipotent differentiation capacity, and the two human airway epithelial cell lines, Calu-3 and CFBE. The data demonstrate that exposure of airway epithelial cells to IL-8 and IL-13, two cytokines known to be enhanced in CF and asthma, respectively, leads to an increase in mucus production. Expression of MUC5AC was fully dependent on expression of TMEM16A, as shown by siRNA knockdown of TMEM16A. In addition, different inhibitors of TMEM16A attenuated IL-13-induced mucus production. Interestingly, in CFBE cells expressing F508 delCFTR, IL-13 was unable to upregulate membrane expression of TMEM16A or Ca2+-activated whole cell currents. The regulator of TMEM16A, CLCA1, strongly augmented both Ca2+- and cAMP-activated Cl2 currents in cells expressing wtCFTR but failed to augment membrane expression of TMEM16A in F508 delCFTR-expressing CFBE cells. The data confirm the functional relationship between CFTR and TMEM16A and suggest an impaired upregulation of TMEM16A by IL-13 or CLCA1 in cells expressing the most frequent CF-causing mutation F508 delCFTR.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ION-TRANSPORT; ASTHMA; DIFFERENTIATION; BICARBONATE; EXPRESSION; PROTEIN; ANO1; LINE; CFTR; TMEM16A; anoctamin 1; airway epithelium; asthma; cystic fibrosis |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Aug 2022 10:05 |
| Last Modified: | 02 Aug 2022 10:05 |
| URI: | https://pred.uni-regensburg.de/id/eprint/46007 |
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