{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T08:34:12Z","timestamp":1723106052766},"reference-count":40,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2015,7,14]],"date-time":"2015-07-14T00:00:00Z","timestamp":1436832000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["SFRH\/BD\/73660\/2010"],"award-info":[{"award-number":["SFRH\/BD\/73660\/2010"]}]},{"name":"ON.2 SR&TD Integrated Program","award":["N-01-01-01-24-01-07, UMINHO\/BPD\/31\/2013"],"award-info":[{"award-number":["N-01-01-01-24-01-07, UMINHO\/BPD\/31\/2013"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Retinoic acid (RA) and ghrelin levels are altered in human hypoplastic lungs when compared to healthy lungs. Although considerable data have been obtained about RA, ghrelin and bombesin in the congenital diaphragmatic hernia (CDH) rat model, neuroendocrine factors have never been associated with the RA signalling pathway in this animal model.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In this study, the interaction between neuroendocrine factors and RA was explored in the CDH rat model.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The authors found that normal fetal lung explants treated with RA, bombesin and ghrelin showed an increase in lung growth. Hypoplastic lungs presented higher expression levels of the RA receptors \u03b1 and \u03b3. Moreover bombesin and ghrelin supplementation, <jats:italic>in vitro<\/jats:italic>, to normal lungs increased RA receptor \u03b1\/\u03b3 expression whereas administration of bombesin and ghrelin antagonists to normal and hypoplastic lungs decreased it.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These data reveal for the first time that there is a link between neuroendocrine factors and RA, and that neuroendocrine factors sensitise the lung to the RA action through RA receptor modulation.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Congenital diaphragmatic hernia (CDH) is characterised by a spectrum of lung hypoplasia and consequent pulmonary hypertension, leading to high morbidity and mortality rates. Moreover, CDH has been associated with an increase in the levels of pulmonary neuroendocrine factors, such as bombesin and ghrelin, and a decrease in the action of retinoic acid (RA). The present study aimed to elucidate the interaction between neuroendocrine factors and RA. <jats:italic>In vitro<\/jats:italic> analyses were performed on Sprague\u2013Dawley rat embryos. Normal lung explants were treated with bombesin, ghrelin, a bombesin antagonist, a ghrelin antagonist, dimethylsulfoxide (DMSO), RA dissolved in DMSO, bombesin plus RA and ghrelin plus RA. Hypoplastic lung explants (nitrofen model) were cultured with bombesin, ghrelin, bombesin antagonist or ghrelin antagonist. The lung explants were analysed morphometrically, and retinoic acid receptor (RAR) \u03b1, \u03b2 and \u03b3 expression levels were assessed via Western blotting. Immunohistochemistry analysis of RAR was performed in normal and hypoplastic lungs 17.5\u00a0days post\u2010conception (dpc). Compared with the controls, hypoplastic lungs exhibited significantly higher RAR\u03b1\/\u03b3 expression levels. Furthermore considering hypoplastic lungs, bombesin and ghrelin antagonists decreased RAR\u03b1\/\u03b3 expression. Normal lung explants (13.5\u00a0dpc) treated with RA, bombesin plus RA, ghrelin plus RA, bombesin or ghrelin exhibited increased lung growth. Moreover, bombesin and ghrelin increased RAR\u03b1\/\u03b3 expression levels, whereas the bombesin and ghrelin antagonists decreased RAR\u03b1\/\u03b3 expression. This study demonstrates for the first time that neuroendocrine factors function as lung growth regulators, sensitising the lung to the action of RA through up\u2010regulation of RAR\u03b1 and RAR\u03b3.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp270477","type":"journal-article","created":{"date-parts":[[2015,6,19]],"date-time":"2015-06-19T23:54:04Z","timestamp":1434758044000},"page":"3301-3311","source":"Crossref","is-referenced-by-count":16,"title":["Neuroendocrine factors regulate retinoic acid receptors in normal and hypoplastic lung development"],"prefix":"10.1113","volume":"593","author":[{"given":"Patr\u00edcia","family":"Pereira\u2010Terra","sequence":"first","affiliation":[{"name":"Life and Health Sciences Research Institute, School of Health Sciences University of Minho  Braga Portugal"},{"name":"Life and Health Sciences Research Institute\/3B's \u2013 PT Government Associate Laboratory  Braga\/Guimar\u00e3es Portugal"}]},{"given":"Rute S.","family":"Moura","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute, School of Health Sciences University of Minho  Braga Portugal"},{"name":"Life and Health Sciences Research Institute\/3B's \u2013 PT Government Associate Laboratory  Braga\/Guimar\u00e3es Portugal"}]},{"given":"Cristina","family":"Nogueira\u2010Silva","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute, School of Health Sciences University of Minho  Braga Portugal"},{"name":"Life and Health Sciences Research Institute\/3B's \u2013 PT Government Associate Laboratory  Braga\/Guimar\u00e3es Portugal"},{"name":"Department of Obstetrics and Gynecology Hospital de Braga  Braga Portugal"}]},{"given":"Jorge","family":"Correia\u2010Pinto","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute, School of Health Sciences University of Minho  Braga Portugal"},{"name":"Life and Health Sciences Research Institute\/3B's \u2013 PT Government Associate Laboratory  Braga\/Guimar\u00e3es Portugal"},{"name":"Department of Pediatric Surgery Hospital de Braga  Braga Portugal"}]}],"member":"311","published-online":{"date-parts":[[2015,7,14]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"888","article-title":"Incidence of congenital diaphragmatic hernia in the young of rats bred on a diet deficient in vitamin A","volume":"62","author":"Andersen DH","year":"1941","journal-title":"Am J Dis Child"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1998.275.6.L1184"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02483031"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/71.5.1325s"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00403.2003"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2005.01.034"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20370"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1753-4887.2009.00247.x"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/neu.20242"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1159\/000068932"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.2350\/07-04-0267.1"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00383-010-2654-x"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjsurg.2005.05.035"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(93)90367-T"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200907-1126OC"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/PL00007644"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpc.12508"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2004.057547"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s003830050399"},{"key":"e_1_2_6_21_1","doi-asserted-by":"crossref","first-page":"2749","DOI":"10.1242\/dev.120.10.2749","article-title":"Function of the retinoic acid receptors (RARs) during development. 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