{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:26:52Z","timestamp":1791206812831,"version":"4.1.0"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2011,2,1]],"date-time":"2011-02-01T00:00:00Z","timestamp":1296518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>The respiratory epithelium has a remarkable capacity to respond to acute injury. In contrast, repeated epithelial injury is often associated with abnormal repair, inflammation, and fibrosis. There is increasing evidence that nonciliated epithelial cells play important roles in the repair of the bronchiolar epithelium after acute injury. Cellular processes underlying the repair and remodeling of the lung after chronic epithelial injury are poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To identify cell processes mediating epithelial regeneration and remodeling after acute and chronic Clara cell depletion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A transgenic mouse model was generated to conditionally express diphtheria toxin A to ablate Clara cells in the adult lung. Epithelial regeneration and peribronchiolar fibrosis were assessed after acute and chronic Clara cell depletion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Acute Clara cell ablation caused squamous metaplasia of ciliated cells and induced proliferation of residual progenitor cells. Ciliated cells in the bronchioles and pro\u2013surfactant protein C\u2013expressing cells in the bronchiolar alveolar duct junctions did not proliferate. Epithelial cell proliferation occurred at multiple sites along the airways and was not selectively associated with regions around neuroepithelial bodies. Chronic Clara cell depletion resulted in ineffective repair and caused peribronchiolar fibrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Colocalization of proliferation and cell type\u2013specific markers demonstrate that Clara cells are critical airway progenitor cells. Continuous depletion of Clara cells resulted in persistent squamous metaplasia, lack of normal reepithelialization, and peribronchiolar fibrosis. Induction of proliferation in subepithelial fibroblasts supports the concept that chronic epithelial depletion caused peribronchiolar fibrosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201005-0744oc","type":"journal-article","created":{"date-parts":[[2010,9,24]],"date-time":"2010-09-24T22:50:44Z","timestamp":1285368644000},"page":"511-521","source":"Crossref","is-referenced-by-count":78,"title":["Conditional Depletion of Airway Progenitor Cells Induces Peribronchiolar Fibrosis"],"prefix":"10.1093","volume":"183","author":[{"given":"Anne-Karina T.","family":"Perl","sequence":"first","affiliation":[{"name":"Division of Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter","family":"Riethmacher","sequence":"additional","affiliation":[{"name":"Human Genetics Division, University of Southampton, School of Medicine, Southampton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A.","family":"Whitsett","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,2,15]]},"reference":[{"key":"2026032504243505600_BIB1","first-page":"L800","volume-title":"Am J Physiol","year":"1995"},{"key":"2026032504243505600_BIB2","first-page":"L1256","volume-title":"Am J Physiol Lung Cell Mol Physiol","year":"2000"},{"key":"2026032504243505600_BIB3","first-page":"269","volume-title":"Am J Pathol","year":"2000"},{"key":"2026032504243505600_BIB4","first-page":"648","volume-title":"Lab Invest","year":"1978"},{"key":"2026032504243505600_BIB5","first-page":"14703","volume-title":"J Biol Chem","year":"1992"},{"key":"2026032504243505600_BIB6","first-page":"671","volume-title":"Am J Respir Cell Mol Biol","year":"2001"},{"key":"2026032504243505600_BIB7","first-page":"525","volume-title":"Cell Stem Cell","year":"2009"},{"key":"2026032504243505600_BIB8","first-page":"1899","volume-title":"Development","year":"2009"},{"key":"2026032504243505600_BIB9","first-page":"153","volume-title":"Transl Res","year":"2009"},{"key":"2026032504243505600_BIB10","first-page":"1007","volume-title":"Eur Respir J","year":"2003"},{"key":"2026032504243505600_BIB11","first-page":"367","volume-title":"Am J Respir Cell Mol Biol","year":"2005"},{"key":"2026032504243505600_BIB12","first-page":"2645","volume-title":"N Engl J Med","year":"2004"},{"key":"2026032504243505600_BIB13","first-page":"136","volume-title":"Ann Intern Med","year":"2001"},{"key":"2026032504243505600_BIB14","first-page":"558","volume-title":"Lab Invest","year":"1976"},{"key":"2026032504243505600_BIB15","first-page":"185","volume-title":"Am J Pathol","year":"1974"},{"key":"2026032504243505600_BIB16","first-page":"254","volume-title":"Am J Respir Crit Care Med","year":"2010"},{"key":"2026032504243505600_BIB17","first-page":"L525","volume-title":"Am J Physiol Lung Cell Mol Physiol","year":"2007"},{"key":"2026032504243505600_BIB18","first-page":"A2388","volume-title":"Am J Respir Crit Care Med","year":"2009"},{"key":"2026032504243505600_BIB19","first-page":"455","volume-title":"Am J Respir Cell Mol Biol","year":"2005"},{"key":"2026032504243505600_BIB20","first-page":"519","volume-title":"Am J Respir Cell Mol Biol","year":"2006"},{"key":"2026032504243505600_BIB21","first-page":"322","volume-title":"Genesis","year":"2006"},{"key":"2026032504243505600_BIB22","first-page":"977","volume-title":"Eukaryot Cell","year":"2009"},{"key":"2026032504243505600_BIB23","first-page":"21","volume-title":"Transgenic Res","year":"2002"},{"key":"2026032504243505600_BIB24","first-page":"1183","volume-title":"J Histochem Cytochem","year":"1996"},{"key":"2026032504243505600_BIB25","first-page":"167","volume-title":"Genesis","year":"2008"},{"key":"2026032504243505600_BIB26","first-page":"469","volume-title":"Genesis","year":"2009"},{"key":"2026032504243505600_BIB27","first-page":"915","volume-title":"Nat Genet","year":"2008"},{"key":"2026032504243505600_BIB28","first-page":"549","volume-title":"J Exp Med","year":"2009"},{"key":"2026032504243505600_BIB29","first-page":"7636","volume-title":"Mol Cell Biol","year":"2004"},{"key":"2026032504243505600_BIB30","first-page":"1","volume-title":"Am J Respir Cell Mol Biol","year":"2009"},{"key":"2026032504243505600_BIB31","first-page":"211","volume-title":"Immunity","year":"2002"},{"key":"2026032504243505600_BIB32","first-page":"2941","volume-title":"J Am Soc Nephrol","year":"2005"},{"key":"2026032504243505600_BIB33","first-page":"151","volume-title":"Am J Respir Cell Mol Biol","year":"2006"},{"key":"2026032504243505600_BIB34","first-page":"410","volume-title":"Proc Natl Acad Sci USA","year":"2007"},{"key":"2026032504243505600_BIB35","first-page":"173","volume-title":"Am J Pathol","year":"2002"},{"key":"2026032504243505600_BIB36","first-page":"823","volume-title":"Cell","year":"2005"},{"key":"2026032504243505600_BIB37","first-page":"L152","volume-title":"Am J Physiol Lung Cell Mol Physiol","year":"2008"},{"key":"2026032504243505600_BIB38","first-page":"3","volume-title":"Am J Pathol","year":"2009"},{"key":"2026032504243505600_BIB39","first-page":"123","volume-title":"Drug Resist Updat","year":"2008"},{"key":"2026032504243505600_BIB40","first-page":"481","volume-title":"Histochem Cell Biol","year":"2008"},{"key":"2026032504243505600_BIB41","first-page":"L231","volume-title":"Am J Physiol Lung Cell Mol Physiol","year":"2008"},{"key":"2026032504243505600_BIB42","first-page":"12771","volume-title":"Proc Natl Acad Sci USA","year":"2009"},{"key":"2026032504243505600_BIB43","first-page":"e8248","volume-title":"PLoS ONE","year":"2009"},{"key":"2026032504243505600_BIB44","first-page":"662","volume-title":"Am J Respir Cell Mol Biol","year":"2001"},{"key":"2026032504243505600_BIB45","first-page":"126","volume-title":"Am J Pathol","year":"1986"},{"key":"2026032504243505600_BIB46","first-page":"487","volume-title":"Pathol Res Pract","year":"1999"},{"key":"2026032504243505600_BIB47","first-page":"527","volume-title":"J Pathol","year":"2002"},{"key":"2026032504243505600_BIB48","first-page":"121","volume-title":"Methods","year":"2008"},{"key":"2026032504243505600_BIB49","first-page":"74","volume-title":"Mol Pharmacol","year":"1995"},{"key":"2026032504243505600_BIB50","first-page":"791","volume-title":"Drug Metab Rev","year":"2002"},{"key":"2026032504243505600_BIB51","first-page":"9286","volume-title":"Proc Natl Acad Sci USA","year":"2009"},{"key":"2026032504243505600_BIB52","first-page":"577","volume-title":"Am J Pathol","year":"2004"},{"key":"2026032504243505600_BIB53","first-page":"1","volume-title":"Am J Respir Cell Mol Biol","year":"2001"},{"key":"2026032504243505600_BIB54","first-page":"39","volume-title":"Lab Invest","year":"1982"},{"key":"2026032504243505600_BIB55","first-page":"463","volume-title":"Histol Histopathol","year":"1996"},{"key":"2026032504243505600_BIB56","first-page":"13180","volume-title":"Proc Natl Acad Sci USA","year":"2006"},{"key":"2026032504243505600_BIB57","first-page":"L741","volume-title":"Am J Physiol Lung Cell Mol Physiol","year":"2004"},{"key":"2026032504243505600_BIB58","first-page":"1633","volume-title":"Am J Pathol","year":"2006"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/183\/4\/511\/67504406\/ajrccm_183_4_511.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/183\/4\/511\/67504406\/ajrccm_183_4_511.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T08:25:04Z","timestamp":1774427104000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/183\/4\/511\/8514761"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,2]]},"references-count":58,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2011,2,15]]},"published-print":{"date-parts":[[2011,2,15]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.201005-0744oc","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2011,2]]},"published":{"date-parts":[[2011,2]]}}}