Cystic adenomatoid malformations are induced by localized FGF10 overexpression in fetal rat lung
Autor(a) principal: | |
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Data de Publicação: | 2008 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/61467 |
Resumo: | 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. |
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Cystic adenomatoid malformations are induced by localized FGF10 overexpression in fetal rat lungAdenoviridaeAnimalsBase SequenceCystic Adenomatoid Malformation of Lung, CongenitalDNA PrimersFemaleFetusFibroblast Growth Factor 10Genetic VectorsGreen Fluorescent ProteinsImmunohistochemistryIn Situ HybridizationLungMagnetic Resonance ImagingPhenotypePolymerase Chain ReactionPregnancyRNA, MessengerRatsRats, Sprague-DawleyAdenoviral vectorLung developmentGene transfercongenital cystic adenomatoid malformationScience & TechnologyFibroblast 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.This project was in part funded by proceeds from the Ruth and Tristram C. Colket Jr. Chair in Pediatric Surgery (A.W.F.), and the Fundação para a Ciência e Tecnologia (POCI/SAUOBS/56428/2004). S.G. was supported by FCT grant ref. SFRH/BD/15260/2004.American Thoracic SocietyUniversidade do MinhoGonzaga, SílviaHenriques-Coelho, TiagoDavey, MarcusZoltick, Philip W.Leite-Moreira, Adelino F.Correia-Pinto, JorgeFlake, Alan W.2008-092008-09-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/61467eng1044-15491535-498910.1165/rcmb.2007-0290OC18421016info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:36:32Zoai:repositorium.sdum.uminho.pt:1822/61467Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:32:39.507182Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Cystic adenomatoid malformations are induced by localized FGF10 overexpression in fetal rat lung |
title |
Cystic adenomatoid malformations are induced by localized FGF10 overexpression in fetal rat lung |
spellingShingle |
Cystic adenomatoid malformations are induced by localized FGF10 overexpression in fetal rat lung Gonzaga, Sílvia Adenoviridae 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 Science & Technology |
title_short |
Cystic adenomatoid malformations are induced by localized FGF10 overexpression in fetal rat lung |
title_full |
Cystic adenomatoid malformations are induced by localized FGF10 overexpression in fetal rat lung |
title_fullStr |
Cystic adenomatoid malformations are induced by localized FGF10 overexpression in fetal rat lung |
title_full_unstemmed |
Cystic adenomatoid malformations are induced by localized FGF10 overexpression in fetal rat lung |
title_sort |
Cystic adenomatoid malformations are induced by localized FGF10 overexpression in fetal rat lung |
author |
Gonzaga, Sílvia |
author_facet |
Gonzaga, Sílvia Henriques-Coelho, Tiago Davey, Marcus Zoltick, Philip W. Leite-Moreira, Adelino F. Correia-Pinto, Jorge Flake, Alan W. |
author_role |
author |
author2 |
Henriques-Coelho, Tiago Davey, Marcus Zoltick, Philip W. Leite-Moreira, Adelino F. Correia-Pinto, Jorge Flake, Alan W. |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Gonzaga, Sílvia Henriques-Coelho, Tiago Davey, Marcus Zoltick, Philip W. Leite-Moreira, Adelino F. Correia-Pinto, Jorge Flake, Alan W. |
dc.subject.por.fl_str_mv |
Adenoviridae 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 Science & Technology |
topic |
Adenoviridae 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 Science & Technology |
description |
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. |
publishDate |
2008 |
dc.date.none.fl_str_mv |
2008-09 2008-09-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/61467 |
url |
http://hdl.handle.net/1822/61467 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1044-1549 1535-4989 10.1165/rcmb.2007-0290OC 18421016 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
American Thoracic Society |
publisher.none.fl_str_mv |
American Thoracic Society |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799132839571095552 |