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Pediatric Surgery International

, Volume 27, Issue 2, pp 125–129 | Cite as

Prenatal retinoic acid treatment upregulates late gestation lung protein 1 in the nitrofen-induced hypoplastic lung in late gestation

  • Elke Maria Ruttenstock
  • Takashi Doi
  • Jens Dingemann
  • Prem Puri
Original Article

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusion

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.

Keywords

Congenital diaphragmatic hernia (CDH) Nitrofen Pulmonary hypoplasia (PH) Retinoic acid (RA) Late gestational lung protein 1 (LGL1) 

Notes

Acknowledgments

The authors thank Prof. Feige Kaplan from the Departments of Human Genetics, Pediatrics and Biology at McGill University, Montreal, QC, Canada, for their excellent technical support, providing us with the LGL1 antibody.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Elke Maria Ruttenstock
    • 1
  • Takashi Doi
    • 1
    • 2
  • Jens Dingemann
    • 1
  • Prem Puri
    • 1
    • 2
  1. 1.National Children’s Research CentreOur Lady’s Children’s HospitalDublin 12Ireland
  2. 2.School of Medicine and Medical Science, Conway Institute of Biomolecular and Biomedical ResearchUniversity College DublinDublinIreland

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