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Ruttenstock, EM; Doi, T; Dingemann, J; Puri, P.
Prenatal retinoic acid treatment upregulates late gestation lung protein 1 in the nitrofen-induced hypoplastic lung in late gestation.
Pediatr Surg Int. 2011; 27(2):125-129 Doi: 10.1007/s00383-010-2783-2
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Leading authors Med Uni Graz: Ruttenstock Elke Maria
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Abstract:: Pulmonary hypoplasia (PH), the leading cause of mortality in congenital diaphragmatic hernia (CDH), is associated with arrested alveolarization. Late gestation lung protein 1 (LGL1) plays a crucial role in the regulation of alveolarization. Inhibition of LGL1 impairs alveolar maturation in fetal rat lungs. LGL1 heterozygotus knockout mice display delayed lung maturation. It is well known that prenatal administration of retinoic acid (RA) stimulates alveologenesis in nitrofen-induced PH. In vitro studies have reported that RA is a key modulator of LGL1 during alveologenesis. We hypothesized, that pulmonary gene expression of LGL1 is downregulated in the late stage of lung development, and that prenatal administration of RA upregulates pulmonary LGL1 expression in the nitrofen CDH model. Pregnant rats were exposed to nitrofen on day 9 (D9) of gestation. RA was given intraperitoneally on D18, D19 and D20. Fetal lungs were dissected on D21 and divided into control, control + RA, CDH and CDH + RA group. Expression levels of LGL1 were determined using RT-PCR and immunohistochemistry. On D21, LGL1 relative mRNA expression levels were significantly downregulated in CDH group compared to controls. After RA treatment, gene expression levels of LGL1 were significantly upregulated in CDH + RA and control + RA compared to CDH group. Immunohistochemical studies confirmed these results. Downregulation of pulmonary LGL1 gene expression in the late stage of lung development may interfere with normal alveologenesis. Upregulation of LGL1 pulmonary gene expression after RA treatment may promote lung growth by stimulating alveologenesis in the nitrofen CDH model.
Find related publications in this database (using NLM MeSH Indexing): Animals -; Female -; Gene Expression Regulation, Developmental - drug effects; Gestational Age -; Hernia, Diaphragmatic - chemically induced; Immunohistochemistry -; Lung - abnormalities; Lung Diseases - chemically induced; Phenyl Ethers - toxicity; Pregnancy -; Pregnancy, Animal -; Proteins - genetics; RNA, Messenger - biosynthesis; Rats -; Reverse Transcriptase Polymerase Chain Reaction -; Tretinoin - administration and dosage
Find related publications in this database (Keywords): Congenital diaphragmatic hernia (CDH); Nitrofen; Pulmonary hypoplasia (PH); Retinoic acid (RA); Late gestational lung protein 1 (LGL1)