{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:26:08Z","timestamp":1787160368073,"version":"build-2736575974"},"reference-count":67,"publisher":"The Company of Biologists","issue":"3","license":[{"start":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T00:00:00Z","timestamp":1644192000000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81970019"],"award-info":[{"award-number":["81970019"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100013262","name":"State Key Laboratory of Respiratory Disease","doi-asserted-by":"crossref","award":["SKLRD-OP-202110"],"award-info":[{"award-number":["SKLRD-OP-202110"]}],"id":[{"id":"10.13039\/100013262","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Guangdong Key Research and Development Project","award":["2020B1111330001"],"award-info":[{"award-number":["2020B1111330001"]}]},{"name":"Zhongnanshan Medical Foundation of Guangdong Province","award":["ZNSA-2020001"],"award-info":[{"award-number":["ZNSA-2020001"]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["KFO309"],"award-info":[{"award-number":["KFO309"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["284237345"],"award-info":[{"award-number":["284237345"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002794","name":"Cancerfonden","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Max-Planck-Gesellschaft"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,2,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The tracheal epithelium is a primary target for pulmonary diseases as it provides a conduit for air flow between the environment and the lung lobes. The cellular and molecular mechanisms underlying airway epithelial cell proliferation and differentiation remain poorly understood. Hedgehog (HH) signaling orchestrates communication between epithelial and mesenchymal cells in the lung, where it modulates stromal cell proliferation, differentiation and signaling back to the epithelium. Here, we reveal a previously unreported autocrine function of HH signaling in airway epithelial cells. Epithelial cell depletion of the ligand sonic hedgehog (SHH) or its effector smoothened (SMO) causes defects in both epithelial cell proliferation and differentiation. In cultured primary human airway epithelial cells, HH signaling inhibition also hampers cell proliferation and differentiation. Epithelial HH function is mediated, at least in part, through transcriptional activation, as HH signaling inhibition leads to downregulation of cell type-specific transcription factor genes in both the mouse trachea and human airway epithelial cells. These results provide new insights into the role of HH signaling in epithelial cell proliferation and differentiation during airway development.<\/jats:p>","DOI":"10.1242\/dev.199804","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T03:11:49Z","timestamp":1643857909000},"source":"Crossref","is-referenced-by-count":15,"title":["An essential function for autocrine hedgehog signaling in epithelial proliferation and differentiation in the trachea"],"prefix":"10.1242","volume":"149","author":[{"given":"Wenguang","family":"Yin","sequence":"first","affiliation":[{"name":"Cardio-Pulmonary Institute, Member of the German Center for Lung Research (DZL), University of Giessen and Marburg Lung Center (UGMLC), Justus Liebig University of Giessen, Giessen 35392, Germany"},{"name":"State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, People's Republic of China"},{"name":"Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL), Bad Nauheim 61231, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Liontos","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, S-10691 Stockholm, Sweden"},{"name":"Science for Life Laboratory, Stockholm University, Solna 171 21, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine","family":"Koepke","sequence":"additional","affiliation":[{"name":"Cardio-Pulmonary Institute, Member of the German Center for Lung Research (DZL), University of Giessen and Marburg Lung Center (UGMLC), Justus Liebig University of Giessen, Giessen 35392, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maroua","family":"Ghoul","sequence":"additional","affiliation":[{"name":"Cardio-Pulmonary Institute, Member of the German Center for Lung Research (DZL), University of Giessen and Marburg Lung Center (UGMLC), Justus Liebig University of Giessen, Giessen 35392, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana","family":"Mazzocchi","sequence":"additional","affiliation":[{"name":"Cardio-Pulmonary Institute, Member of the German Center for Lung Research (DZL), University of Giessen and Marburg Lung Center (UGMLC), Justus Liebig University of Giessen, Giessen 35392, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyuan","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyu","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanasios","family":"Fysikopoulos","sequence":"additional","affiliation":[{"name":"Cardio-Pulmonary Institute, Member of the German Center for Lung Research (DZL), University of Giessen and Marburg Lung Center (UGMLC), Justus Liebig University of Giessen, Giessen 35392, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandros","family":"Sountoulidis","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, S-10691 Stockholm, Sweden"},{"name":"Science for Life Laboratory, Stockholm University, Solna 171 21, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Werner","family":"Seeger","sequence":"additional","affiliation":[{"name":"Cardio-Pulmonary Institute, Member of the German Center for Lung Research (DZL), University of Giessen and Marburg Lung Center (UGMLC), Justus Liebig University of Giessen, Giessen 35392, Germany"},{"name":"Department of Lung Development and Remodeling, Max Planck Institute for Heart and Lung Research, Bad Nauheim 61231, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemens","family":"Ruppert","sequence":"additional","affiliation":[{"name":"Cardio-Pulmonary Institute, Member of the German Center for Lung Research (DZL), University of Giessen and Marburg Lung Center (UGMLC), Justus Liebig University of Giessen, Giessen 35392, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"G\u00fcnther","sequence":"additional","affiliation":[{"name":"Cardio-Pulmonary Institute, Member of the German Center for Lung Research (DZL), University of Giessen and Marburg Lung Center (UGMLC), Justus Liebig University of Giessen, Giessen 35392, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didier Y. R.","family":"Stainier","sequence":"additional","affiliation":[{"name":"Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL), Bad Nauheim 61231, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christos","family":"Samakovlis","sequence":"additional","affiliation":[{"name":"Cardio-Pulmonary Institute, Member of the German Center for Lung Research (DZL), University of Giessen and Marburg Lung Center (UGMLC), Justus Liebig University of Giessen, Giessen 35392, Germany"},{"name":"Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, S-10691 Stockholm, Sweden"},{"name":"Science for Life Laboratory, Stockholm University, Solna 171 21, Sweden"},{"name":"Department of Lung Development and Remodeling, Max Planck Institute for Heart and Lung Research, Bad Nauheim 61231, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2022,2,7]]},"reference":[{"key":"2022020816153212100_DEV199804C1","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1242\/dev.135681","article-title":"FGFR2 us reguired for airway basal cell self-renewal and terminal differentiation","volume":"144","author":"Balasooriya","year":"2017","journal-title":"Development"},{"key":"2022020816153212100_DEV199804C2","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.jcf.2004.05.010","article-title":"Isolation and air-liquid interface culture of human large airway and bronchiolar epithelial cells","volume":"2","author":"Bals","year":"2004","journal-title":"J. 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