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Pediatric Surgery International

Published in:

01-01-2010 | Original Article

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

Authors: Elke Ruttenstock, Takashi Doi, Jens Dingemann, Prem Puri

Published in: Pediatric Surgery International | Issue 1/2010

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.

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Title: Downregulation of insulin-like growth factor binding protein 3 and 5 in nitrofen-induced pulmonary hypoplasia
Authors: Elke Ruttenstock
Takashi Doi
Jens Dingemann
Prem Puri
Publication date: 01-01-2010
Publisher: Springer-Verlag
Published in: Pediatric Surgery International / Issue 1/2010
Print ISSN: 0179-0358
Electronic ISSN: 1437-9813
DOI: https://doi.org/10.1007/s00383-009-2509-5

At a glance: The STEP trials

Springer Medicine

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

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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