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Injured epithelial cells lose their properties and gain mesenchymal characteristics, a phenotypic switch that contributes to lung remodelling after injury. Here we studied bone morphogenetic protein (<jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content>) signalling and, in particular, the role of <jats:styled-content style=\"fixed-case\">BMP2<\/jats:styled-content> and the <jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content> modulator <jats:styled-content style=\"fixed-case\">BMPER<\/jats:styled-content> in injured lung epithelium. Increased <jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content> activity, reflected by up\u2010regulation of the Smad1\/5\u2013Id1 axis, is detected after injury of lung epithelium <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. Two members of the <jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content> family, <jats:styled-content style=\"fixed-case\">BMP2<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">BMPER<\/jats:styled-content>, have opposing effects. <jats:styled-content style=\"fixed-case\">BMP2<\/jats:styled-content> is up\u2010regulated after epithelial injury and causes epithelial dysfunction and hyperpermeability, mediated by the Smad1\/5\u2013Id1\u2010dependent down\u2010regulation of E\u2010cadherin. In contrast, <jats:styled-content style=\"fixed-case\">BMPER<\/jats:styled-content> expression is decreased following injury, which in turn impairs epithelial integrity, characterized by reduction of E\u2010cadherin and epithelial leakage <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. High levels of <jats:styled-content style=\"fixed-case\">BMPER<\/jats:styled-content> antagonized <jats:styled-content style=\"fixed-case\">BMP2<\/jats:styled-content>\u2010Smad5\u2013Id1 signalling and prevented <jats:styled-content style=\"fixed-case\">BMP2<\/jats:styled-content>\u2010mediated decrease of E\u2010cadherin and hyperpermeability, suggesting that <jats:styled-content style=\"fixed-case\">BMPER<\/jats:styled-content> restores epithelial homeostasis. Supporting this notion, pharmacological inhibition of <jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content> signalling by <jats:styled-content style=\"fixed-case\">LDN193189<\/jats:styled-content> prevented reduction of E\u2010cadherin and disruption of epithelial barrier function. Inhibition of excessive <jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content> activation could be a new approach to restore epithelial integrity and prevent disruption of epithelial barrier function after lung injury. Copyright \u00a9 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:bold><\/jats:p>","DOI":"10.1002\/path.4215","type":"journal-article","created":{"date-parts":[[2013,5,28]],"date-time":"2013-05-28T13:56:22Z","timestamp":1369749382000},"page":"105-116","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Inhibition of <scp>BMP<\/scp> activity protects epithelial barrier function in lung injury"],"prefix":"10.1002","volume":"231","author":[{"given":"Thomas","family":"Helbing","sequence":"first","affiliation":[{"name":"Cardiology and Angiology I, Heart Centre Freiburg University Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva\u2010Maria","family":"Herold","sequence":"additional","affiliation":[{"name":"Cardiology and Angiology I, Heart Centre Freiburg University Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Hornstein","sequence":"additional","affiliation":[{"name":"Cardiology and Angiology I, Heart Centre Freiburg University Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Wintrich","sequence":"additional","affiliation":[{"name":"Cardiology and Angiology I, Heart Centre Freiburg University Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Heinke","sequence":"additional","affiliation":[{"name":"Cardiology and Angiology I, Heart Centre Freiburg University Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Grundmann","sequence":"additional","affiliation":[{"name":"Cardiology and Angiology I, Heart Centre Freiburg University Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cam","family":"Patterson","sequence":"additional","affiliation":[{"name":"Division of Cardiology and McAllister Heart Institute University of North Carolina at Chapel Hill  NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Bode","sequence":"additional","affiliation":[{"name":"Cardiology and Angiology I, Heart Centre Freiburg University Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Moser","sequence":"additional","affiliation":[{"name":"Cardiology and Angiology I, Heart Centre Freiburg University Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,7,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/1753465810396539"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-8-1"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI45961"},{"key":"e_1_2_7_5_1","doi-asserted-by":"crossref","unstructured":"HiraiY NoseA KobayashiS et al.Expression and role of E\u2010 and P\u2010cadherin adhesion molecules in embryonic histogenesis.I. 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