{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T02:15:58Z","timestamp":1740104158737,"version":"3.37.3"},"reference-count":27,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,11,23]],"date-time":"2016-11-23T00:00:00Z","timestamp":1479859200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Science, Sports and Culture","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"name":"JSPS KAKENHI","award":["25462769"],"award-info":[{"award-number":["25462769"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Pulmonology"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Erythropoietin (EPO), an essential stimulator of erythropoiesis produced by the fetal liver, is important both in vascular remodeling and modulation of the endothelial response in the pulmonary vasculature. In addition, EPO guides alveolar development, along with retinoic acid (RA). EPO is a direct target of RA, and the retinoid pathway is altered in the nitrofen\u2010induced congenital diaphragmatic hernia (CDH) model. In the present study, we tested the hypothesis that the synthesis of EPO is suppressed in a rat model of CDH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>Pregnant rats were treated with either nitrofen or vehicle on gestational day 9 (D9). Fetuses were sacrificed on D19 and D21 and divided into control and CDH groups. Immunohistochemistry and quantitative real\u2010time polymerase chain reaction (RT\u2010PCR) were performed to determine the expression of EPO in the fetal liver and kidney. We also estimated the expression of EPO receptor in the fetal lung.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The relative EPO mRNA expression in the liver on D19 and in the kidney on D21 were significantly lower in the CDH group than in the controls (<jats:italic>P<\/jats:italic>\u2009=\u20090.0008 and <jats:italic>P<\/jats:italic>\u2009=\u20090.0064, respectively). In addition, the results of immunohistochemistry supported the findings from the RT\u2010PCR analysis. No significant changes were noted in the expression pattern or EPO receptor levels in the fetal lungs of the CDH group compared to the controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results reveal the suppressed EPO synthesis in the CDH fetus, which may contribute to the pathogenesis of lung hypoplasia and modification of pulmonary vasculature in the CDH rat model. <jats:bold>Pediatr Pulmonol. 2017;52:606\u2013615.<\/jats:bold> \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ppul.23640","type":"journal-article","created":{"date-parts":[[2016,11,23]],"date-time":"2016-11-23T17:24:42Z","timestamp":1479921882000},"page":"606-615","source":"Crossref","is-referenced-by-count":5,"title":["Suppressed erythropoietin expression in a nitrofen\u2010induced congenital diaphragmatic hernia"],"prefix":"10.1002","volume":"52","author":[{"given":"Hajime","family":"Takayasu","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery, Faculty of Medicine University of Tsukuba 1\u20101\u20101 Tennoudai Tsukuba Ibaraki 305\u20108575 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koki","family":"Hagiwara","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Faculty of Medicine University of Tsukuba 1\u20101\u20101 Tennoudai Tsukuba Ibaraki 305\u20108575 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kouji","family":"Masumoto","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Faculty of Medicine University of Tsukuba 1\u20101\u20101 Tennoudai Tsukuba Ibaraki 305\u20108575 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