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. 2024 Jun;70(6):527-530.
doi: 10.1165/rcmb.2023-0419LE.

Increased Expression of ATP12A in Small Airway Epithelia of Post-COVID-19 Pulmonary Fibrosis

Mohamed Abdelgied  1 , Shan Zhou  2 , Katie Uhl  1 , Tara Jager  3 , Cameron Lawson  3 , David Chesla  4 , Edward Murphy  3 , Kun Li  2 , Reda E Girgis  3 , Xiaopeng Li  1
Affiliations

Increased Expression of ATP12A in Small Airway Epithelia of Post-COVID-19 Pulmonary Fibrosis

Mohamed Abdelgied et al. Am J Respir Cell Mol Biol. 2024 Jun.
No abstract available

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Figures

Figure 1.
Figure 1.
ATP12A upregulation in the small airways of post–coronavirus disease (COVID-19) pulmonary fibrosis (PF) and idiopathic PF (IPF) is associated with increased small airway mucus accumulation. (A) Representative confocal microscopy images showing immunodetection of ATP12A (red) in the small airways by immunofluorescence. Nuclei were counterstained with DAPI (blue). Scale bar, 25 μm. (B) Bright-field microscopy images show ATP12A mRNA detection (red, black arrows) by in situ hybridization. Nuclei were counterstained with hematoxylin (light blue). Scale bar, 100 μm. (C) Confocal microscopy images showing immunodetection of MUC5B (red) and MUC5AC (green) by immunofluorescence. Nuclei were counterstained with DAPI (blue). Scale bar, 25 μm. (D) ATP12A immunofluorescence staining intensity quantification chart. Data are expressed as mean ± SD of 12 normal, 7 post–COVID-19 PF, and 11 IPF lung samples. ATP12A expression intensities were quantified in more than five small airways per donor. (E) Charts show the percentage of small airway obstruction in 11 normal, 7 post–COVID-19 PF, and 11 IPF lung samples. Data are expressed as mean ± SD. The percentage of small airway mucus obstruction was measured as the area occupied by mucus (i.e., MUC5B) within the total area of the small airways in lung sections. (F and G) Charts show the correlation between ATP12A staining intensity and the degree of small airway mucus obstruction in post–COVID-19 PF and IPF. (H) Confocal microscopy images showing immunodetection of Atp12a (red) in the small airways of mice by immunofluorescence. Nuclei were counterstained with DAPI (blue). Scale bars, 50 μm. (I) Bright-field microscopy images show Atp12a mRNA detection (red, black arrows) by in situ hybridization in mouse lungs. Nuclei were counterstained with hematoxylin (light blue). Scale bars: top and bottom panel, 100 μm; middle panel, 500 μm. (J) Confocal microscopy images showing immunodetection of Muc5b (red) in the small airways by immunofluorescence. Nuclei were counterstained with DAPI (blue). Scale bars, 50 μm. (K) Confocal microscopy images showing immunodetection of ATP12A (red) and Muc5B (green) in mouse airways by immunofluorescence. Nuclei were counterstained with DAPI (blue). Scale bars, 50 μm. (L) Atp12a immunofluorescence staining intensity quantification chart in mouse lung airways. Data are expressed as mean ± SD of four negative controls and six SARS-CoV-2–infected mice. On the images, “COVID-19” indicates post–COVID-19 pulmonary fibrosis. **P < 0.01 versus normal lung, ***P < 0.001 versus normal lung, #P < 0.05 versus IPF, and ##P < 0.01 versus IPF. NL = normal lung.
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References

    1. Singh SJ, Baldwin MM, Daynes E, Evans RA, Greening NJ, Jenkins RG, et al. Respiratory sequelae of COVID-19: pulmonary and extrapulmonary origins, and approaches to clinical care and rehabilitation. Lancet Respir Med . 2023;11:709–725. - PMC - PubMed
    1. Verleden SE, Tanabe N, McDonough JE, Vasilescu DM, Xu F, Wuyts WA, et al. Small airways pathology in idiopathic pulmonary fibrosis: a retrospective cohort study. Lancet Respir Med . 2020;8:573–584. - PMC - PubMed
    1. Cherrez-Ojeda I, Osorio MF, Robles-Velasco K, Calderón JC, Cortés-Télles A, Zambrano J, et al. Small airway disease in post-acute COVID-19 syndrome, a non-conventional approach in three years follow-up of a patient with long COVID: a case report. J Med Case Reports . 2023;17:386. - PMC - PubMed
    1. Shah VS, Meyerholz DK, Tang XX, Reznikov L, Abou Alaiwa M, Ernst SE, et al. Airway acidification initiates host defense abnormalities in cystic fibrosis mice. Science . 2016;351:503–507. - PMC - PubMed
    1. Abdelgied M, Uhl K, Chen OG, Schultz C, Tripp K, Peraino AM, et al. Targeting atp12a, a non-gastric proton pump alpha subunit, for idiopathic pulmonary fibrosis treatment. Am J Respir Cell Mol Biol . 2023;68:638–650. - PMC - PubMed

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