{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T09:05:06Z","timestamp":1791104706990,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,7,30]],"date-time":"2014-07-30T00:00:00Z","timestamp":1406678400000},"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":[[2014,8]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Caveolin\u20101 (Cav\u20101) exerts major regulatory functions on intracellular signaling pathways originating at the plasma membrane. Cav\u20101 is a key regulator in adverse lung remodeling and the development of pulmonary hypertension (PH) regulating vasomotor tone through its ability to reduce nitric oxide (NO) production. This low\u2010output endothelial NO synthase (eNOS) derived NO maintains normal pulmonary vascular homeostasis. Cav\u20101 deficiency leads to increased bioavailability of NO, which has been linked to increased nitrosative stress. Inhibition of eNOS reduced oxidant production and reversed PH, supporting the concept that Cav\u20101 regulation of eNOS activity is crucial to endothelial homeostasis in lungs. We designed this study to investigate the hypothesis that expression of Cav\u20101 is downregulated while eNOS expression is upregulated by the pulmonary endothelium in the nitrofen\u2010induced congenital diaphragmatic hernia (CDH).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Pregnant rats were exposed to nitrofen or vehicle on day 9.5 (D9.5). Fetuses were sacrificed on D21 and divided into nitrofen and control groups. Quantitative real\u2010time polymerase chain reaction, Western blotting, and confocal immunofluorescence were performed to determine pulmonary gene expression levels and protein expression of Cav\u20101 and eNOS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Pulmonary <jats:italic>Cav\u20101<\/jats:italic> gene expression levels were significantly decreased, while <jats:italic>eNOS<\/jats:italic> gene expression was significantly increased in nitrofen\u2010induced CDH(+). Western blotting and confocal microscopy revealed decreased pulmonary Cav\u20101 protein expression, while eNOS protein expression was increased in CDH(+) compared to controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The striking evidence of markedly decreased gene and protein expression of Cav\u20101 with concurrently increased eNOS gene and protein expression in the pulmonary vasculature suggests that activation of eNOS secondary to Cav\u20101 deficiency may play an important role in the pathogenesis of PH in the nitrofen\u2010induced CDH<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdrb.21117","type":"journal-article","created":{"date-parts":[[2014,7,31]],"date-time":"2014-07-31T01:23:03Z","timestamp":1406769783000},"page":"341-346","source":"Crossref","is-referenced-by-count":16,"title":["Imbalance of Caveolin\u20101 and eNOS Expression in the Pulmonary Vasculature of Experimental Diaphragmatic Hernia"],"prefix":"10.1002","volume":"101","author":[{"given":"Alejandro","family":"Hofmann","sequence":"first","affiliation":[{"name":"National Children's Research Centre Our Lady's Children's Hospital  Gate 5 Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan\u2010Hendrik","family":"Gosemann","sequence":"additional","affiliation":[{"name":"National Children's Research Centre Our Lady's Children's Hospital  Gate 5 Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiaki","family":"Takahashi","sequence":"additional","affiliation":[{"name":"National Children's Research Centre Our Lady's Children's Hospital  Gate 5 Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Friedmacher","sequence":"additional","affiliation":[{"name":"National Children's Research Centre Our Lady's Children's Hospital  Gate 5 Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes W.","family":"Duess","sequence":"additional","affiliation":[{"name":"National Children's Research Centre Our Lady's Children's Hospital  Gate 5 Dublin Ireland"},{"name":"School of Medicine and Medical Science and Conway Institute of Biomedical Research University College Dublin  Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prem","family":"Puri","sequence":"additional","affiliation":[{"name":"National Children's Research Centre Our Lady's Children's Hospital  Gate 5 Dublin Ireland"},{"name":"School of Medicine and Medical Science and Conway Institute of Biomedical Research University College Dublin  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