Increased expression of ATP12A proton pump in cystic fibrosis airways

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 Jv Galietta

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
JournalJCI insight
Volume3
Issue number20
DOIs
Publication statusPublished - Oct 18 2018

Keywords

  • Animals
  • Bronchi/cytology
  • Cell Membrane/metabolism
  • Cells, Cultured
  • Colon/cytology
  • Cystic Fibrosis/immunology
  • Goblet Cells/immunology
  • H(+)-K(+)-Exchanging ATPase/genetics
  • Humans
  • Hydrogen-Ion Concentration
  • Interleukin-4/immunology
  • Mice
  • Mice, Knockout
  • Ouabain/pharmacology
  • Permeability
  • Potassium/metabolism
  • Primary Cell Culture
  • Proton Pump Inhibitors/pharmacology
  • Sodium-Potassium-Exchanging ATPase/metabolism

Fingerprint

Dive into the research topics of 'Increased expression of ATP12A proton pump in cystic fibrosis airways'. Together they form a unique fingerprint.

Cite this