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https://hdl.handle.net/1822/58156
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Campo DC | Valor | Idioma |
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dc.contributor.author | Khoshgoo, Naghmeh | por |
dc.contributor.author | Kholdebarin, Ramin | por |
dc.contributor.author | Terra, Patrícia Daniela Pereira | por |
dc.contributor.author | Mahood, Thomas H. | por |
dc.contributor.author | Falk, Landon | por |
dc.contributor.author | Day, Chelsea A. | por |
dc.contributor.author | Iwasiow, Barbara M. | por |
dc.contributor.author | Zhu, Fuqin | por |
dc.contributor.author | Mulhall, Drew | por |
dc.contributor.author | Fraser, Carly | por |
dc.contributor.author | Correia-Pinto, Jorge | por |
dc.contributor.author | Keijzer, Richard | por |
dc.date.accessioned | 2019-01-14T15:19:31Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | Khoshgoo, N., Kholdebarin, R., Pereira-Terra, P., Mahood, T. H., Falk, L., Day, C. A., ... & Correia-Pinto, J. (2019). Prenatal microRNA miR-200b Therapy Improves Nitrofen-induced Pulmonary Hypoplasia Associated With Congenital Diaphragmatic Hernia. Annals of surgery | por |
dc.identifier.issn | 0003-4932 | - |
dc.identifier.uri | https://hdl.handle.net/1822/58156 | - |
dc.description | Epub ahead of print | por |
dc.description.abstract | We aimed to evaluate the use of miR-200b as a prenatal transplacental therapy in the nitrofen rat model of abnormal lung development and congenital diaphragmatic hernia (CDH).Background:Pulmonary hypoplasia (PH) and pulmonary hypertension determine mortality and morbidity in CDH babies. There is no safe medical prenatal treatment available. We previously discovered that higher miR-200b is associated with better survival in CDH babies. Here, we investigate the role of miR-200b in the nitrofen rat model of PH and CDH and evaluate its use as an in vivo prenatal therapy.Methods:We profiled miR-200b expression during nitrofen-induced PH using RT-qPCR and in situ hybridization in the nitrofen rat model of PH and CDH. The effects of nitrofen on downstream miR-200b targets were studied in bronchial lung epithelial cells using a SMAD luciferase assay, Western blotting and Immunohistochemistry. We evaluated miR-200b as a lung growth promoting therapy ex vivo and in vivo using lung explant culture and transplacental prenatal therapy in the nitrofen rat model.Results:We show that late lung hypoplasia in CDH is associated with (compensatory) upregulation of miR-200b in less hypoplastic lungs. Increasing miR-200b abundance with mimics early after nitrofen treatment decreases SMAD-driven TGF-β signaling and rescues lung hypoplasia both in vitro and in vivo. Also, prenatal miR-200b therapy decreases the observed incidence of CDH.Conclusions:Our data indicate that miR-200b improves PH and decreases the incidence of CDH. Future studies will further exploit this newly discovered prenatal therapy for lung hypoplasia and CDH. | eng |
dc.description.abstract | Objective: We aimed to evaluate the use of miR-200b as a prenatal transplacental therapy in the nitrofen rat model of abnormal lung development and congenital diaphragmatic hernia (CDH). Background: Pulmonary hypoplasia (PH) and pulmonary hypertension determine mortality and morbidity in CDH babies. There is no safe medical prenatal treatment available. We previously discovered that higher miR-200b is associated with better survival in CDH babies. Here, we investigate the role of miR-200b in the nitrofen rat model of PH and CDH and evaluate its use as an in vivo prenatal therapy. Methods: We profiled miR-200b expression during nitrofen-induced PH using RT-qPCR and in situ hybridization in the nitrofen rat model of PH and CDH. The effects of nitrofen on downstream miR-200b targets were studied in bronchial lung epithelial cells using a SMAD luciferase assay, Western blotting and Immunohistochemistry. We evaluated miR-200b as a lung growth promoting therapy ex vivo and in vivo using lung explant culture and transplacental prenatal therapy in the nitrofen rat model. Results: We show that late lung hypoplasia in CDH is associated with (compensatory) upregulation of miR-200b in less hypoplastic lungs. Increasing miR-200b abundance with mimics early after nitrofen treatment decreases SMAD-driven TGF-β signaling and rescues lung hypoplasia both in vitro and in vivo. Also, prenatal miR-200b therapy decreases the observed incidence of CDH. Conclusions: Our data indicate that miR-200b improves PH and decreases the incidence of CDH. Future studies will further exploit this newly discovered prenatal therapy for lung hypoplasia and CDH | por |
dc.description.sponsorship | CCHCSP -Manitoba Lung Association(undefined) | por |
dc.language.iso | eng | por |
dc.publisher | Wolters Kluwer Health | por |
dc.rights | closedAccess | por |
dc.subject | Congenital diaphragmatic hernia | por |
dc.subject | Lung hypoplasia | por |
dc.subject | microRNA | por |
dc.subject | miR-200b | por |
dc.subject | Prenatal therapy | por |
dc.title | Prenatal microRNA miR-200b Therapy Improves Nitrofen-induced Pulmonary Hypoplasia Associated With Congenital Diaphragmatic Hernia | por |
dc.type | article | por |
dc.peerreviewed | yes | por |
dc.relation.publisherversion | https://journals.lww.com/annalsofsurgery/Abstract/publishahead/Prenatal_microRNA_miR_200b_Therapy_Improves.95830.aspx | por |
oaire.citationStartPage | 979 | por |
oaire.citationEndPage | 987 | por |
oaire.citationIssue | 5 | por |
oaire.citationVolume | 269 | por |
dc.identifier.doi | 10.1097/SLA.0000000000002595 | por |
dc.identifier.pmid | 29135495 | por |
dc.subject.fos | Ciências Médicas::Medicina Básica | por |
dc.description.publicationversion | info:eu-repo/semantics/acceptedVersion | por |
sdum.journal | Annals of Surgery | por |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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khoshgoo2017.pdf Acesso restrito! | 1,76 MB | Adobe PDF | Ver/Abrir |