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Increased expression of ATP12A proton pump in cystic fibrosis airways
Paolo Scudieri, … , Gilles Crambert, Luis J.V. Galietta
Paolo Scudieri, … , Gilles Crambert, Luis J.V. Galietta
Published October 18, 2018
Citation Information: JCI Insight. 2018;3(20):e123616. https://doi.org/10.1172/jci.insight.123616.
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Research Article Pulmonology

Increased expression of ATP12A proton pump in cystic fibrosis airways

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Abstract

Proton secretion mediated by ATP12A protein on the surface of the airway epithelium may contribute to cystic fibrosis (CF) lung disease by favoring bacterial infection and airway obstruction. We studied ATP12A in fresh bronchial samples and in cultured epithelial cells. In vivo, ATP12A expression was found almost exclusively at the apical side of nonciliated cells of airway epithelium and in submucosal glands, with much higher expression in CF samples. This could be due to bacterial infection and inflammation, since treating cultured cells with bacterial supernatants or with IL-4 (a cytokine that induces goblet cell hyperplasia) increased the expression of ATP12A in nonciliated cells. This observation was associated with upregulation and translocation of ATP1B1 protein from the basal to apical epithelial side, where it colocalizes with ATP12A. ATP12A function was evaluated by measuring the pH of the apical fluid in cultured epithelia. Under resting conditions, CF epithelia showed more acidic values. This abnormality was minimized by inhibiting ATP12A with ouabain. Following treatment with IL-4, ATP12A function was markedly increased, as indicated by strong acidification occurring under bicarbonate-free conditions. Our study reveals potentially novel aspects of ATP12A and remarks its importance as a possible therapeutic target in CF and other respiratory diseases.

Authors

Paolo Scudieri, Ilaria Musante, Emanuela Caci, Arianna Venturini, Patrizia Morelli, Christine Walter, Davide Tosi, Alessandro Palleschi, Pablo Martin-Vasallo, Isabelle Sermet-Gaudelus, Gabrielle Planelles, Gilles Crambert, Luis J.V. Galietta

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Figure 5

ATP12A-ATP1B1 colocalization in bronchial epithelial cells.

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ATP12A-ATP1B1 colocalization in bronchial epithelial cells.
(A) Represen...
(A) Representative xy and xz confocal images showing immunodetection of ATP12A and ATP1B1 in cultured bronchial epithelial cells under control condition (top) or after treatment with IL-4 for 72 hours (bottom). Scale bar: 20 μm and 10 μm for xy and xz images, respectively. Images were collected from 3 separate preparations on non-CF cells and 2 preparations on CF cells. (B) Representative images taken by confocal xz scans (top) and Elyra superresolution xy scans (bottom) from cultured bronchial epithelial cells treated with IL-4. Images show colocalization of ATP12A and ATP1B1 in the apical membrane (apical plane) but not in the basolateral compartment (basal plane). Scale bar: 5 μm. (C) Representative images showing colocalization of ATP12A and ATP1B1 in CF bronchial samples. Scale bar: 10 μm.

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