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Down-regulation of Wnt signal pathway in nitrofen-induced hypoplastic lung

Hajime Takayasu1, Nana Nakazawa, Sandra Montedonico

  • 1Children's Research Centre, Our Lady's Hospital for Sick Children, Dublin, University College Dublin, 12 Dublin, Ireland.

Journal of Pediatric Surgery
|February 3, 2007
PubMed
Abstract

Insights

Wnt signaling pathway down-regulation in early lung development is linked to nitrofen-induced pulmonary hypoplasia. Reduced GATA6 expression may cause this Wnt pathway disruption, impacting lung morphogenesis.

Area of Science:

  • Developmental biology
  • Molecular biology
  • Genetics

Background:

  • Congenital diaphragmatic hernia (CDH) is associated with pulmonary hypoplasia, a condition with poorly understood pathogenesis.
  • The Wnt signaling pathway is crucial for lung branching morphogenesis.
  • Wnt7b gene deficiency in mice leads to severe lung hypoplasia and respiratory failure.

Purpose of the Study:

  • To investigate alterations in Wnt-mediated signaling in nitrofen-induced hypoplastic lungs.
  • To examine the expression of Wnt genes (Wnt7b, Wnt2) and a Wnt target gene (BMP4) in normal and nitrofen-treated rat lungs.

Main Methods:

  • Fetal rat lungs were harvested at embryonic days E15, E17, E19, and E21.
  • Gene expression analysis using real-time reverse transcription polymerase chain reaction (RT-PCR).
  • Quantification of GATA6, Wnt7b, Wnt2, and BMP4 expression levels.

Main Results:

  • Significant reduction in Wnt7b, Wnt2, and BMP4 gene expression in nitrofen-treated lungs at E15 (P < .05).
  • Significantly decreased GATA6 expression in the nitrofen group (P < .05).
  • GATA6 is known to transactivate Wnt7b expression.

Conclusions:

  • The Wnt signaling pathway is down-regulated in early stages of nitrofen-induced hypoplastic lungs.
  • Decreased GATA6 expression may underlie the Wnt pathway down-regulation.
  • Down-regulation of Wnt signaling likely disrupts lung morphogenesis, leading to pulmonary hypoplasia in this CDH model.

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