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https://hdl.handle.net/1822/40569
Título: | Neuroendocrine factors regulate retinoic acid receptors in normal and hypoplastic lung development |
Autor(es): | Terra, Patrícia Daniela Pereira Moura, Rute S. Silva, Cristina Nogueira Pinto, Jorge Correia |
Data: | 2015 |
Editora: | The Physiological Society |
Revista: | The Journal of Physiology |
Citação: | Pereira-Terra, P., Moura, R. S., Nogueira-Silva, C., & Correia-Pinto, J. (2015). Neuroendocrine factors regulate retinoic acid receptors in normal and hypoplastic lung development. Journal of Physiology-London, 593(15), 3301-3311. doi: 10.1113/jp270477 |
Resumo(s): | 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. In vitro analyses were performed on Sprague-Dawley 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) α, β and γ expression levels were assessed via Western blotting. Immunohistochemistry analysis of RAR was performed in normal and hypoplastic lungs 17.5 days post-conception (dpc). Compared with the controls, hypoplastic lungs exhibited significantly higher RARα/γ expression levels. Furthermore considering hypoplastic lungs, bombesin and ghrelin antagonists decreased RARα/γ expression. Normal lung explants (13.5 dpc) treated with RA, bombesin plus RA, ghrelin plus RA, bombesin or ghrelin exhibited increased lung growth. Moreover, bombesin and ghrelin increased RARα/γ expression levels, whereas the bombesin and ghrelin antagonists decreased RARα/γ 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-regulation of RARα and RARγ. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/40569 |
DOI: | 10.1113/jp270477 |
ISSN: | 0022-3751 1469-7793 |
Versão da editora: | http://onlinelibrary.wiley.com/doi/10.1113/JP270477/abstract |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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pereira-terra_et_al-2015-the_journal_of_physiology.pdf | 1,18 MB | Adobe PDF | Ver/Abrir |