Inhibition of ATP12A by potassium-competitive proton pump blocker VON reduced BLEO-induced alveolar epithelium apoptosis, airway mucus accumulation, and honeycomb cyst formation in mice expressing ATP12A. (A) Confocal microscope images show cellular apoptosis of lung epithelial cells by TUNEL staining. Apoptotic cell nuclei are stained green. Scale bars, 25 μm. (B) The chart shows the percentage of apoptotic cells in mouse lungs. Data are expressed as mean ± SD. n ⩾ 5 animals per group. (C) Confocal microscope images show the immunodetection of MUC5B (red) and MUC5AC (green) by immunofluorescence. Nuclei were counterstained by DAPI (blue). Scale bars, 25 μm. (D) The chart shows airway mucus thickness in mouse lungs. Data are expressed as mean ± SD. n ⩾ 5 animals per group. (E) Confocal microscope images show immunodetection of keratin 5 (Krt5, basal cell marker in green) by immunofluorescence. The inset shows a honeycomb cyst (white asterisk) with Krt5 + cell lining (green). Nuclei were counterstained by DAPI (blue). Scale bars, 25 μm. (F) The chart shows the number of honeycomb cysts per right middle lung lobe (column chart) and the average diameter of honeycomb cysts (linear plot). Data are expressed as mean ± SD. n ⩾ 3 animals per group. ***P < 0.001 compared to CTL; ###P < 0.001 compared to B+ATP12A+VON.