{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T06:53:30Z","timestamp":1767855210464,"version":"3.49.0"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,2,19]],"date-time":"2013-02-19T00:00:00Z","timestamp":1361232000000},"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":[[2013,4]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>The molecular mechanisms underlying the diaphragmatic defect in congenital diaphragmatic hernia (<jats:styled-content style=\"fixed-case\">CDH<\/jats:styled-content>) are still poorly understood. The transcription factor <jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content>4 is essential for normal development of the diaphragm. Recently, mutations in the <jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content>4 gene have been linked to human and rodent <jats:styled-content style=\"fixed-case\">CDH<\/jats:styled-content>. We hypothesized that diaphragmatic <jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content>4 expression is downregulated in the nitrofen <jats:styled-content style=\"fixed-case\">CDH<\/jats:styled-content> model.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Pregnant rats received Nitrofen or vehicle on day 9 of gestation (<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>9). Fetuses were sacrificed on <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>13, <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>18, or <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>21. Pleuroperitoneal folds (<jats:italic>n<\/jats:italic> = 20) and fetal diaphragms (<jats:italic>n<\/jats:italic> = 40) were (micro) dissected and divided into <jats:styled-content style=\"fixed-case\">CDH<\/jats:styled-content> group and controls. <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> and protein were extracted. <jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content>4 m<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> levels were determined by real\u2010time <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>. Protein levels were determined by <jats:styled-content style=\"fixed-case\">ELISA<\/jats:styled-content> and Immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>m<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> levels and Protein levels were significantly decreased in the <jats:styled-content style=\"fixed-case\">CDH<\/jats:styled-content> group compared to controls on <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>13 (m<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> 15.96 \u00b1 6.99 vs. 38.10 \u00b1 5.01, <jats:italic>p<\/jats:italic> &lt; 0.05), <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>18 (m<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> 10.45 \u00b1 1.84 vs. 17.68 \u00b1 2.11, Protein 2.59 \u00b1 0.06 vs. 4.58 \u00b1 0.35 <jats:italic>p<\/jats:italic> &lt; 0.05) and D21 (m<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> 4.31 \u00b1 0.83 vs. 6.87 \u00b1 0.88, Protein 0.16 \u00b1 0.08 vs. 1.26 \u00b1 0.49, <jats:italic>p<\/jats:italic> &lt; 0.05). Immunoreactivity of <jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content>4 was markedly decreased in <jats:styled-content style=\"fixed-case\">CDH<\/jats:styled-content>\u2010diaphragms on <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>13, <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>18, and <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>21.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>We provide evidence for the first time that diaphragmatic expression of <jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content>4 is downregulated in the nitrofen model, suggesting that decreased expression of <jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content>4 may impair diaphragmatic development in nitrofen\u2010induced <jats:styled-content style=\"fixed-case\">CDH<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdrb.21037","type":"journal-article","created":{"date-parts":[[2007,12,18]],"date-time":"2007-12-18T22:16:22Z","timestamp":1198016182000},"page":"139-143","source":"Crossref","is-referenced-by-count":9,"title":["Decreased Expression of <scp>GATA<\/scp>4 in the Diaphragm of Nitrofen\u2010Induced Congenital Diaphragmatic Hernia"],"prefix":"10.1002","volume":"98","author":[{"given":"Jens","family":"Dingemann","sequence":"first","affiliation":[{"name":"National Children's Research Centre Our Lady's Children's Hospital Dublin Ireland"},{"name":"Centre of Pediatric Surgery Hannover Hannover Medical School and Bult Children's Hospital Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Doi","sequence":"additional","affiliation":[{"name":"National Children's Research Centre Our Lady's Children's Hospital Dublin Ireland"},{"name":"University College Dublin Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan\u2010Hendrik","family":"Gosemann","sequence":"additional","affiliation":[{"name":"National Children's Research Centre Our Lady's Children's Hospital Dublin Ireland"},{"name":"Centre of Pediatric Surgery Hannover Hannover Medical School and Bult Children's Hospital Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elke Maria","family":"Ruttenstock","sequence":"additional","affiliation":[{"name":"National Children's Research Centre Our Lady's Children's Hospital Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nana","family":"Nakazawa","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":"University College Dublin Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,2,19]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.13.4.2235"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0401833101"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.sempedsurg.2007.01.004"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00027.2008"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2009-0076OC"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20613"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2009.04.027"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0223(1998100)18:10<1055::AID-PD405>3.0.CO;2-I"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1203\/01.PDR.0000062660.12769.E6"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2008.01212.x"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1086\/513442"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2006.09.050"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.30132"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.sempedsurg.2010.03.001"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.11.8.1048"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.1468"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00383-005-1593-4"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30778"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.028787"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.112.3.532"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2003.10.002"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-3468(90)90386-N"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2007.10.047"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32896"}],"container-title":["Birth Defects Research Part B: Developmental and Reproductive 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