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

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–mese...

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Bibliographic Details
Published in:Pediatric surgery international 2013-11, Vol.29 (11), p.1193-1198
Main Authors: Friedmacher, Florian, Gosemann, Jan-Hendrik, Fujiwara, Naho, Takahashi, Hiromizu, Hofmann, Alejandro, Puri, Prem
Format: Article
Language:English
Subjects:
Abnormalities, Multiple - chemically induced
Abnormalities, Multiple - genetics
Abnormalities, Multiple - metabolism
Animals
Disease Models, Animal
Female
Fibroblast Growth Factors - antagonists & inhibitors
Gene Expression Regulation, Developmental
Immunohistochemistry
Lung - abnormalities
Lung - embryology
Lung - metabolism
Lung Diseases - chemically induced
Lung Diseases - genetics
Lung Diseases - metabolism
MAP Kinase Signaling System
Medicine
Medicine & Public Health
Morphogenesis - genetics
Nerve Tissue Proteins - biosynthesis
Nerve Tissue Proteins - genetics
Original Article
Pediatric Surgery
Pediatrics
Phenyl Ethers - toxicity
Pregnancy
Pregnancy, Animal
Rats
Rats, Sprague-Dawley
Real-Time Polymerase Chain Reaction
Repressor Proteins - biosynthesis
Repressor Proteins - genetics
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
Surgery
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Summary: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  
ISSN:0179-0358
1437-9813
DOI:10.1007/s00383-013-3385-6