Prenatal treatment with retinoic acid activates parathyroid hormone-related protein signaling in the nitrofen-induced hypoplastic lung
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Takashi Doi • Kaoru Sugimoto • Elke Ruttenstock • Jens Dingemann • Prem Puri
- چاپ و سال / کشور: 2011
Description
Purpose Prenatal treatment with retinoic acid (RA) has been reported to stimulate alveologenesis in hypoplastic lungs (HL) in the nitrofen model of congenital diaphragmatic hernia (CDH). Parathyroid hormone-related protein (PTHrP) promotes alveolar maturation by stimulating surfactant production, regulated by PTHrP receptor (PTHrP-R). PTHrP knockout and PTHrP-R null mice both exhibit pulmonary hypoplasia. We have recently reported that nitrofen inhibits PTHrP signaling in the nitrofen-induced HL. Because both PTHrP and PTHrP-R genes have RAinducible element, we hypothesized that prenatal administration of RA upregulates pulmonary gene expression of PTHrP and PTHrP-R in the nitrofen-induced HL. Methods Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). RA was given on days D18, D19 and D20. Fetal lungs were obtained on D21 and divided into four groups: control, control ? RA, nitrofen, nitrofen ? RA. RT-PCR and Immunohistochemistry were performed to investigate the pulmonary PTHrP and PTHrPR gene and protein expression in each group, respectively. Results The pulmonary gene expression levels of PTHrP and PTHrP-R were significantly increased in nitrofen ? RA group compared to nitrofen group (p\0.05). Immunoreactivity of PTHrP and PTHrP-R was also remarkably increased in nitrofen ? RA group compared to nitrofen group. Conclusions Upregulation of PTHrP and PTHrP-R genes after prenatal treatment with RA in the nitrofen-induced HL suggests that RA may have a therapeutic potential in reverting lung hypoplasia in CDH, by stimulating surfactant production and alveolar maturation.
Pediatr Surg Int (2011) 27:47–52 DOI 10.1007/s00383-010-2726-y Published online: 21 September 2010
