{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T00:12:34Z","timestamp":1782519154068,"version":"3.54.5"},"reference-count":22,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,8,19]],"date-time":"2020-08-19T00:00:00Z","timestamp":1597795200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Pulmonology"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hypoxia and asphyxia are known to induce surfactant inactivation in newborns. Deleted in Malignant Brain Tumors 1 (DMBT1) is an innate immunity protein with functions in epithelial differentiation and angiogenesis. It was detected in hyaline membranes of infants with respiratory distress syndrome. Human recombinant DMBT1 is able to increase the surface tension of exogenous surfactant preparations in a dose\u2010dependent manner.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Immunohistochemistry was performed on lung sections of infants who died due to pre\u2010, peri\u2010 or postnatal hypoxia. The lung epithelial cell line A549 was stably transfected with a DMBT1 (DMBT1+ cells) expression plasmid or with an empty plasmid (DMBT1\u2212 cells). The cells were cultured in normoxic or hypoxic conditions, and then DMBT1 as well as HIF\u20101\u03b1 RNA expression were analyzed by using real\u2010time\u2010polymerase chain reaction. Human recombinant DMBT1 was added to the modified porcine natural surfactant Curosurf to examine the effect of DMBT1 on surfactant ultrastructure with electron microscopy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>DMBT1 expression was upregulated in human lung tissue after fetal\/peri\u2010\/postnatal hypoxia. In addition, in vitro experiments showed increased DMBT1 RNA expression in A549 cells after hypoxia. HIF\u20101\u03b1 was upregulated in both DMBT1+ and DMBT1\u2212 cells in response to hypoxia. The addition of human recombinant DMBT1 to Curosurf caused an impaired surfactant ultrastructure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>DMBT1 is upregulated in response to hypoxia and there seems to be a link between hypoxia and surfactant inactivation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ppul.25018","type":"journal-article","created":{"date-parts":[[2020,8,8]],"date-time":"2020-08-08T16:06:18Z","timestamp":1596902778000},"page":"2964-2969","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["DMBT1 is upregulated in lung epithelial cells after hypoxia and changes surfactant ultrastructure"],"prefix":"10.1002","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7804-4711","authenticated-orcid":false,"given":"Hanna","family":"M\u00fcller","sequence":"first","affiliation":[{"name":"Division of Neonatology and Pediatric Intensive Care, Department of Pediatrics, University Hospital Erlangen University of Erlangen\u2010N\u00fcrnberg Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Schmiedl","sequence":"additional","affiliation":[{"name":"Institute of Functional and Applied Anatomy Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christel","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department for Medical Statistics and Biomathematics University Hospital Mannheim Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Ai","sequence":"additional","affiliation":[{"name":"Division of Neonatology and Pediatric Intensive Care, Department of Pediatrics, University Hospital Erlangen University of Erlangen\u2010N\u00fcrnberg Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Hospital Erlangen University of Erlangen\u2010N\u00fcrnberg Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Renner","sequence":"additional","affiliation":[{"name":"Institute of Pathology University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,19]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.161.6.9908014"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.160.2.9809060"},{"key":"e_1_2_7_4_1","first-page":"225","article-title":"Morphological studies of the lungs in chronic hypobaric hypoxia","volume":"48","author":"Sulkowska M","year":"1997","journal-title":"Pol J 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