Prenatal retinoic acid upregulates pulmonary gene expression of PI3K and AKT in nitrofen-induced pulmonary hypoplasia.

Pediatric Surgery International
Takashi DoiPrem Puri

Abstract

The precise mechanism of pulmonary hypoplasia associated with congenital diaphragmatic hernia (CDH) still remains unclear. Recently, prenatal treatment with retinoic acid (RA) has been reported to stimulate alveologenesis in hypoplastic lungs in the nitrofen model of CDH. The serine/threonine protein kinase B (AKT) plays a key role in lung morphogenesis through epithelial-mesenchymal interaction in phosphatidylinositide 3-kinase (PI3K)-dependent manner. It has been reported that the lung morphogenesis in explants in mice is interfered by inhibitors of PI3K-AKT signaling pathway. Furthermore, we have recently shown that nitrofen inhibits PI3K-AKT signaling during mid-to-late lung morphogenesis in the nitrofen-induced hypoplastic lung. We hypothesized that prenatal administration of RA upregulates pulmonary gene expression of PI3K and AKT in the nitrofen-induced hypoplastic lung. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). 5 mg/kg of RA was given on D18, D19 and D20. The fetuses were harvested on D21, and fetal lungs were obtained and divided into four groups: control, control + RA, nitrofen, nitrofen + RA. The mRNA expression levels of PI3K and AKT were analyzed in each lung by real-tim...Continue Reading

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Citations

Jan 25, 2011·Pediatric Surgery International·Elke Maria RuttenstockPrem Puri
May 10, 2011·Revue des maladies respiratoires·A LabbéP-J Déchelotte
Jun 23, 2015·The Journal of Physiology·Patrícia Pereira-TerraJorge Correia-Pinto
Mar 20, 2016·Pediatric Surgery International·Augusto Frederico SchmidtLourenço Sbragia
Apr 12, 2015·Pediatric Surgery International·Patrícia Pereira-TerraRichard Keijzer

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