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Insulinlike growth factor receptor type 1 and type 2 are downregulated in the nitrofen-induced hypoplastic lung

Elke Ruttenstock1, Takashi Doi, Jens Dingemann

  • 1The Children's Research Center, Our Lady's Children's Hospital, Dublin 12, Ireland; University College Dublin, Dublin 4, Ireland.

Journal of Pediatric Surgery
|July 13, 2010
PubMed
Abstract

Insights

Congenital diaphragmatic hernia (CDH) is linked to lung hypoplasia. This study found that insulin-like growth factor receptors 1 and 2 (IGF-1R and IGF-2R) gene expression is reduced in a CDH rat model, suggesting a role in lung development impairment.

Area of Science:

  • Developmental biology
  • Genetics
  • Pulmonology

Background:

  • Congenital diaphragmatic hernia (CDH) is associated with high mortality due to severe pulmonary hypoplasia.
  • Insulin-like growth factor receptor type 1 (IGF-1R) and type 2 (IGF-2R) are crucial for lung alveologenesis.
  • IGF-1R null mutation and IGF-2R knockout mice exhibit respiratory failure and retarded lung development, respectively.

Purpose of the Study:

  • To investigate the hypothesis that IGF-1R and IGF-2R gene expression levels are downregulated in a nitrofen-induced CDH model.
  • To assess the role of IGF-1R and IGF-2R in the pathogenesis of pulmonary hypoplasia in CDH.

Main Methods:

  • Pregnant rats were administered nitrofen or olive oil on day 9.5 of gestation.
  • Fetal tissues were harvested on days 18 and 21 for analysis.
  • Relative mRNA levels of IGF-1R and IGF-2R were quantified using real-time RT-PCR, and protein expression was determined by immunohistochemistry.

Main Results:

  • Significant downregulation of IGF-1R mRNA levels was observed in the nitrofen-induced CDH group compared to controls on day 21 (P < .05).
  • IGF-2R mRNA levels were also significantly decreased in the nitrofen group on day 21 (P < .05).
  • Immunohistochemistry confirmed reduced protein expression of both IGF-1R and IGF-2R in the nitrofen-induced CDH model.

Conclusions:

  • Downregulation of IGF-1R and IGF-2R gene expression is implicated in the impaired alveologenesis observed in the nitrofen-induced CDH model.
  • These findings suggest that altered IGF-1R and IGF-2R expression contributes to pulmonary hypoplasia in CDH.

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