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Downregulation of insulin-like growth factor binding protein 3 and 5 in nitrofen-induced pulmonary hypoplasia

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

Abstract

Purpose

The high mortality in congenital diaphragmatic hernia (CDH) is mainly attributed to pulmonary hypoplasia. Recent studies suggest that retinoid signaling pathway (RSP) is inhibited in the nitrofen-induced hypoplastic lung. The insulin-like growth factor (IGF) system plays a crucial role in fetal lung development by interaction of IGFBP-3 and IGFBP-5 with RSP. We hypothesized that pulmonary IGFBP-3 and IGFBP-5 gene expression levels are downregulated in the nitrofen-induced pulmonary hypoplasia.

Methods

Pregnant rats were exposed to either olive oil or 100 mg nitrofen on day 9.5 (D9.5) of gestation. Fetal lungs were harvested on D18 and D21 and divided into control and nitrofen groups. IGFBP-3 and IGFBP-5 pulmonary gene and protein expression were determined using real-time RT–PCR and immunohistochemistry.

Results

Relative levels of IGFBP-3 mRNA were significantly decreased in the nitrofen group (8.00 ± 14.44) in D21 compared to controls (14.81 ± 16.11; p < 0.05). Expression levels of IGFBP-5 mRNA were also significantly decreased in nitrofen group (10.66 ± 4.83) on D18 compared to controls (17.92 ± 4.77). Immunohistochemistry showed decreased IGFBP-3 expression on D21 and decreased IGFBP-5 immunoreactivity on D18 in hypoplastic lungs compared to controls.

Conclusion

Downregulation of IGFBP-3 and IGFBP-5 gene expression may cause pulmonary hypoplasia in the nitrofen-induced CDH model by interfering with retinoid signaling pathway.

Keywords

IGFBP-3 IGFBP-5 Nitrofen Hypoplastic lung Congenital diaphragmatic hernia 

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Elke Ruttenstock
    • 1
  • Takashi Doi
    • 1
  • Jens Dingemann
    • 1
  • Prem Puri
    • 1
  1. 1.The Children’s Research Centre, Our Lady’s Children’s HospitalUniversity College DublinDublin 12Ireland

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