Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Doi, T; Sugimoto, K; Ruttenstock, E; Dingemann, J; Puri, P.
Prenatal treatment with retinoic acid activates parathyroid hormone-related protein signaling in the nitrofen-induced hypoplastic lung.
Pediatr Surg Int. 2011; 27(1):47-52
Doi: 10.1007/s00383-010-2726-y
Web of Science
PubMed
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- Co-authors Med Uni Graz
- Ruttenstock Elke Maria
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- Abstract:
- 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 RA-inducible 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 PTHrP-R 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Analysis of Variance -
- Animals -
- Disease Models, Animal -
- Female -
- Lung - abnormalities
- Lung Diseases - chemically induced
- Parathyroid Hormone-Related Protein - drug effects
- Phenyl Ethers -
- Plant Oils -
- Pregnancy -
- Rats -
- Rats, Sprague-Dawley -
- Reverse Transcriptase Polymerase Chain Reaction -
- Signal Transduction - drug effects
- Tretinoin - pharmacology
- Up-Regulation - drug effects
- Find related publications in this database (Keywords)
- Nitrofen
- Parathyroid hormone-related protein
- Congenital diaphragmatic hernia
- Retinoic acid
- Pulmonary hypoplasia