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The pathogenesis is not clear, and there are currently no effective therapies for IPF. Small airway disease and mucus accumulation are prominent features in IPF lungs, similar to cystic fibrosis lung disease. The ATP12A gene encodes the \u03b1-subunit of the nongastric H+, K+-ATPase, which functions to acidify the airway surface fluid and impairs mucociliary transport function in patients with cystic fibrosis. It is hypothesized that the ATP12A protein may play a role in the pathogenesis of IPF. The authors\u2019 studies demonstrate that ATP12A protein is overexpressed in distal small airways from the lungs of patients with IPF compared with normal human lungs. In addition, overexpression of the ATP12A protein in mouse lungs worsened bleomycin induced experimental pulmonary fibrosis. This was prevented by a potassium competitive proton pump blocker, vonoprazan. These data support the concept that the ATP12A protein plays an important role in the pathogenesis of lung fibrosis. Inhibition of the ATP12A protein has potential as a novel therapeutic strategy in IPF treatment.<\/jats:p>","DOI":"10.1165\/rcmb.2022-0264oc","type":"journal-article","created":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T17:12:41Z","timestamp":1676308361000},"page":"638-650","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":13,"title":["Targeting ATP12A, a Nongastric Proton Pump \u03b1 Subunit, for Idiopathic Pulmonary Fibrosis Treatment"],"prefix":"10.1093","volume":"68","author":[{"given":"Mohamed","family":"Abdelgied","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Human Development and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Uhl","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Human Development and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver G.","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Human Development and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad","family":"Schultz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Human Development and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaylie","family":"Tripp","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Human Development and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela M.","family":"Peraino","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shreya","family":"Paithankar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Human Development and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Human Development and"},{"name":"Department of Pharmacology and Toxicology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximiliano","family":"Tamae Kakazu","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine"},{"name":"Department of Medicine, College of Human Medicine, Michigan State University, Grand Rapids, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Castillo Bahena","sequence":"additional","affiliation":[{"name":"Research and Development, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara E.","family":"Jager","sequence":"additional","affiliation":[{"name":"Richard Devos Heart and Lung Transplant Program, Spectrum Health, Grand Rapids, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron","family":"Lawson","sequence":"additional","affiliation":[{"name":"Richard Devos Heart and Lung Transplant Program, Spectrum Health, Grand Rapids, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dave W.","family":"Chesla","sequence":"additional","affiliation":[{"name":"Research and Development, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolay","family":"Pestov","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology and Center for Diabetes and Endocrine Research, College of Medicine, University of Toledo, Health Science Campus, Toledo, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolai N.","family":"Modyanov","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology and Center for Diabetes and Endocrine Research, College of Medicine, University of Toledo, Health Science Campus, Toledo, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Prokop","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Human Development and"},{"name":"Department of Pharmacology and Toxicology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard R.","family":"Neubig","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce D.","family":"Uhal","sequence":"additional","affiliation":[{"name":"Department of Physiology, Michigan State University, East Lansing, Michigan; 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