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https://hdl.handle.net/1822/58156
Título: | Prenatal microRNA miR-200b Therapy Improves Nitrofen-induced Pulmonary Hypoplasia Associated With Congenital Diaphragmatic Hernia |
Autor(es): | Khoshgoo, Naghmeh Kholdebarin, Ramin Terra, Patrícia Daniela Pereira Mahood, Thomas H. Falk, Landon Day, Chelsea A. Iwasiow, Barbara M. Zhu, Fuqin Mulhall, Drew Fraser, Carly Correia-Pinto, Jorge Keijzer, Richard |
Palavras-chave: | Congenital diaphragmatic hernia Lung hypoplasia microRNA miR-200b Prenatal therapy |
Data: | 2019 |
Editora: | Wolters Kluwer Health |
Revista: | Annals of Surgery |
Citação: | 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 |
Resumo(s): | 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. 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 |
Tipo: | Artigo |
Descrição: | Epub ahead of print |
URI: | https://hdl.handle.net/1822/58156 |
DOI: | 10.1097/SLA.0000000000002595 |
ISSN: | 0003-4932 |
Versão da editora: | https://journals.lww.com/annalsofsurgery/Abstract/publishahead/Prenatal_microRNA_miR_200b_Therapy_Improves.95830.aspx |
Arbitragem científica: | yes |
Acesso: | Acesso restrito autor |
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 |