{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T15:07:38Z","timestamp":1770995258933,"version":"3.50.1"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,6,18]],"date-time":"2013-06-18T00:00:00Z","timestamp":1371513600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research Pt B"],"published-print":{"date-parts":[[2013,8]]},"abstract":"<jats:sec><jats:title>BACKGROUND\/PURPOSE<\/jats:title><jats:p>Congenital diaphragmatic hernia (CDH) remains a major therapeutic challenge despite advances in neonatal resuscitation and intensive care. The high mortality and morbidity in CDH has been attributed to pulmonary hypoplasia and persistent pulmonary hypertension (PH). Bone morphogenetic protein receptor 2 (BMPR2) plays a key role in pulmonary vasculogenesis during the late stages of fetal lung development. BMPR2 is essential for control of endothelial and smooth muscle cell proliferation. Dysfunction of BMPR2 and downstream signaling have been shown to disturb the crucial balance of proliferation of smooth muscle cells contributing to the pathogenesis of human and experimental PH. We designed this study to investigate the hypothesis that BMPR2 signaling is disrupted in nitrofen\u2010induced CDH.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Pregnant rats were treated with nitrofen or vehicle on gestational day 9 (D9). Fetuses were sacrificed on D21 and divided into CDH and control. Quantitative real\u2010time polymerase chain reaction, Western blotting, and confocal\u2010immunofluorescence were performed to determine pulmonary gene expression levels and protein expression of BMPR2 and related proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Pulmonary <jats:italic>Bmpr2<\/jats:italic> gene expression levels were significantly decreased in nitrofen\u2010induced CDH compared to controls. Western blotting and confocal microscopy revealed decreased pulmonary BMPR2 protein expression and increased activation of p38<jats:sup>MAPK<\/jats:sup> in CDH compared to controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>The observed disruption of the BMPR2 signaling pathway may lead to extensive vascular remodeling and contribute to PH in the nitrofen\u2010induced CDH model. BMPR2 may therefore represent a potential target for the treatment of PH in CDH.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdrb.21065","type":"journal-article","created":{"date-parts":[[2013,6,18]],"date-time":"2013-06-18T19:19:57Z","timestamp":1371583197000},"page":"304-309","source":"Crossref","is-referenced-by-count":18,"title":["Disruption of the Bone Morphogenetic Protein Receptor 2 Pathway in Nitrofen\u2010Induced Congenital Diaphragmatic Hernia"],"prefix":"10.1002","volume":"98","author":[{"given":"Jan\u2010Hendrik","family":"Gosemann","sequence":"first","affiliation":[{"name":"National Children's Research Centre Our Lady's Children's Hospital Dublin Ireland"},{"name":"Department of Pediatric Surgery Hannover Medical School Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian","family":"Friedmacher","sequence":"additional","affiliation":[{"name":"National Children's Research Centre Our Lady's Children's Hospital Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naho","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"National Children's Research Centre Our Lady's Children's Hospital Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis A. J.","family":"Alvarez","sequence":"additional","affiliation":[{"name":"National Children's Research Centre Our Lady's Children's Hospital Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolae","family":"Corcionivoschi","sequence":"additional","affiliation":[{"name":"National Children's Research Centre Our Lady's Children's Hospital Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prem","family":"Puri","sequence":"additional","affiliation":[{"name":"National Children's Research Centre Our Lady's Children's Hospital Dublin Ireland"},{"name":"School of Medicine and Medical Science and Conway Institute of Biomedical Research University College Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,6,18]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.21293"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000012754.72951.3D"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20370"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.197491"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00325.2010"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035364"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00183008"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00034.2007"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00383-011-2987-0"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2012.01.038"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcts.2006.05.026"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00197.2006"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI32503"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1203\/01.pdr.0000233056.37254.0b"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.sempedsurg.2010.03.001"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.845909"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-12-51"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00020.2006"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.13.1517"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)13167-4"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2261"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3468(98)90468-7"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.4103\/2045-8932.78100"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000166926.54293.68"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000156326.48823.55"}],"container-title":["Birth Defects Research Part B: Developmental and Reproductive Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbdrb.21065","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdrb.21065","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T23:35:25Z","timestamp":1696635325000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdrb.21065"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,6,18]]},"references-count":25,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2013,8]]}},"alternative-id":["10.1002\/bdrb.21065"],"URL":"https:\/\/doi.org\/10.1002\/bdrb.21065","archive":["Portico"],"relation":{},"ISSN":["1542-9733","1542-9741"],"issn-type":[{"value":"1542-9733","type":"print"},{"value":"1542-9741","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,6,18]]}}}