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Pediatric Surgery International

Published in:

01-11-2013 | Original Article

Expression of Sproutys and SPREDs is decreased during lung branching morphogenesis in nitrofen-induced pulmonary hypoplasia

Authors: Florian Friedmacher, Jan-Hendrik Gosemann, Naho Fujiwara, Hiromizu Takahashi, Alejandro Hofmann, Prem Puri

Published in: Pediatric Surgery International | Issue 11/2013

Abstract

Purpose

Pulmonary hypoplasia (PH) is a life-threatening condition associated with congenital diaphragmatic hernia (CDH), characterized by defective lung development. Sproutys and Sprouty-related proteins (SPREDs) play a key role in lung branching morphogenesis through modification of epithelial–mesenchymal interactions. During the pseudoglandular stage, Sproutys are highly expressed in distal airway epithelium, while SPREDs within the surrounding mesenchyme. Sprouty2/4 knockouts show severe defects in branching morphogenesis with reduced number of distal airways. SPRED-1 and SPRED-2 are strongly expressed in regions of new airway formation, highlighting their important function in branching pattern. We hypothesized that expression of Sprouty2, Sprouty4, SPRED-1 and SPRED-2 is decreased during lung branching morphogenesis in nitrofen-induced PH.

Methods

Timed-pregnant rats received either nitrofen or vehicle on E9.5. On E15.5 (n = 16), fetal lungs were micro-dissected and divided into controls and PH, while on E18.5 (n = 24) groups were: control, PH without CDH [CDH(−)], and PH with CDH [CDH(+)]. Pulmonary gene expression levels of Sprouty2, Sprouty4, SPRED-1 and SPRED-2 were analyzed by qRT-PCR. Immunohistochemistry was performed to evaluate protein expression/distribution.

Results

On E18.5, relative mRNA expression levels of Sprouty2, Sprouty4, SPRED-1 and SPRED-2 were significantly decreased in CDH(−) and CDH(+) groups compared to controls (P < 0.05). Immunoreactivity of Sprouty2, Sprouty4, SPRED-1 and SPRED-2 was markedly diminished on E18.5 in nitrofen-induced PH.

Conclusion

Decreased expression of Sproutys and SPREDs during the terminal pseudoglandular stage may disrupt lung branching morphogenesis by interfering with epithelial–mesenchymal interactions contributing to PH.

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Title: Expression of Sproutys and SPREDs is decreased during lung branching morphogenesis in nitrofen-induced pulmonary hypoplasia
Authors: Florian Friedmacher
Jan-Hendrik Gosemann
Naho Fujiwara
Hiromizu Takahashi
Alejandro Hofmann
Prem Puri
Publication date: 01-11-2013
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Surgery International / Issue 11/2013
Print ISSN: 0179-0358
Electronic ISSN: 1437-9813
DOI: https://doi.org/10.1007/s00383-013-3385-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Expression of Sproutys and SPREDs is decreased during lung branching morphogenesis in nitrofen-induced pulmonary hypoplasia

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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