Pediatric pulmonology · 2012
Signaling molecules in the fetal rabbit model for congenital diaphragmatic hernia.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Vuckovic Aline, Roubliova Xenia I, Votino Carmela, Naeije Robert, Jani Jacques C
Аннотация
RATIONALE AND OBJECTIVES: Little is known about molecular changes in lungs of fetal rabbits with surgically induced diaphragmatic hernia (DH). Therefore, we examined in this model gene expressions of pivotal molecules for the developing lung.
METHODS: At day 23 of gestation, DH was created in 12 fetuses from 4 does. Both lungs from six live DH fetuses and from six unoperated controls were harvested and weighed at term. Transcription of 15 genes involved in alveolarization, angiogenesis, regulation of vascular tone, or epithelial maturation was investigated by real-time quantitative polymerase chain reaction.
MAIN RESULTS: DH decreased lung-to-body weight ratio (P < 0.001). A bilateral downregulation was seen for genes encoding for tropoelastin (P < 0.01), lysyl oxidase (P < 0.05), fibulin 5 (P < 0.05), and cGMP specific phosphodiesterase 5 (P < 0.05). Lower mRNA levels for endothelial nitric oxide synthase occurred in the ipsilateral lung (P < 0.05).
CONCLUSIONS: Experimental DH in fetal rabbits disrupted transcription of genes implicated in lung growth and function. Similarities with the human disease make this model appropriate for investigation of new prenatal therapies.
METHODS: At day 23 of gestation, DH was created in 12 fetuses from 4 does. Both lungs from six live DH fetuses and from six unoperated controls were harvested and weighed at term. Transcription of 15 genes involved in alveolarization, angiogenesis, regulation of vascular tone, or epithelial maturation was investigated by real-time quantitative polymerase chain reaction.
MAIN RESULTS: DH decreased lung-to-body weight ratio (P < 0.001). A bilateral downregulation was seen for genes encoding for tropoelastin (P < 0.01), lysyl oxidase (P < 0.05), fibulin 5 (P < 0.05), and cGMP specific phosphodiesterase 5 (P < 0.05). Lower mRNA levels for endothelial nitric oxide synthase occurred in the ipsilateral lung (P < 0.05).
CONCLUSIONS: Experimental DH in fetal rabbits disrupted transcription of genes implicated in lung growth and function. Similarities with the human disease make this model appropriate for investigation of new prenatal therapies.
Предметные рубрики MeSH
AnimalsCyclic Nucleotide Phosphodiesterases, Type 5Disease Models, AnimalFemaleFetal Organ MaturityFetusGene Expression ProfilingGene Expression Regulation, DevelopmentalHernia, DiaphragmaticHernias, Diaphragmatic, CongenitalHumansLungNitric Oxide Synthase Type IIIPregnancyProtein-Lysine 6-OxidaseRabbitsSignal TransductionTropoelastin