Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/61467

TitleCystic adenomatoid malformations are induced by localized FGF10 overexpression in fetal rat lung
Author(s)Gonzaga, Sílvia
Henriques-Coelho, Tiago
Davey, Marcus
Zoltick, Philip W.
Leite-Moreira, Adelino F.
Correia-Pinto, Jorge
Flake, Alan W.
KeywordsAdenoviridae
Animals
Base Sequence
Cystic Adenomatoid Malformation of Lung, Congenital
DNA Primers
Female
Fetus
Fibroblast Growth Factor 10
Genetic Vectors
Green Fluorescent Proteins
Immunohistochemistry
In Situ Hybridization
Lung
Magnetic Resonance Imaging
Phenotype
Polymerase Chain Reaction
Pregnancy
RNA, Messenger
Rats
Rats, Sprague-Dawley
Adenoviral vector
Lung development
Gene transfer
congenital cystic adenomatoid malformation
Issue dateSep-2008
PublisherAmerican Thoracic Society
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Abstract(s)Fibroblast growth factor-10 (FGF10) is a mesenchymal growth factor, involved in epithelial and mesenchymal interactions during lung branching morphogenesis. In the present work, FGF10 overexpression was transiently induced in a temporally and spatially restricted manner, during the pseudoglandular or canalicular stages of rat lung development, by trans-uterine ultrasound-guided intraparenchymal microinjections of adenoviral vector encoding the rfgf10 transgene. The morphologic and histologic classification of the resulting malformations were dependent upon developmental stage and location. Overexpression of FGF10 restricted to the proximal tracheobronchial tree during the pseudoglandular phase resulted in large cysts lined by tall columnar epithelium composed primarily of Clara cells with a paucity of Type II pneumocytes, resembling bronchiolar type epithelium. In contrast, FGF10 overexpression in the distal lung parenchyma during the canalicular phase resulted in small cysts lined by cuboidal epithelial cells composed of primarily Type II pneumocytes resembling acinar epithelial differentiation. The cystic malformations induced by FGF10 overexpression appear to closely recapitulate the morphology and histology of the spectrum of human congenital cystic adenomatoid malformation (CCAM). These findings support a role for FGF10 in the induction of human CCAM and provide further mechanistic insight into the role of FGF10 in normal and abnormal lung development.
TypeArticle
URIhttp://hdl.handle.net/1822/61467
DOI10.1165/rcmb.2007-0290OC
ISSN1044-1549
e-ISSN1535-4989
Peer-Reviewedyes
AccessOpen access
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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