| Autor: |
Khoshgoo, Naghmeh, Kholdebarin, Ramin, Pereira-Terra, Patricia, Mahood, Thomas H., Falk, Landon, Day, Chelsea A., Iwasiow, Barbara M., Zhu, Fuqin, Mulhall, Drew, Fraser, Carly, Correia-Pinto, Jorge, Keijzer, Richard |
| Zdroj: |
Annals of Surgery; May2019, Vol. 269 Issue 5, p979-987, 9p |
| Abstrakt: |
Supplemental Digital Content is available in the text 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Supplemental Index |
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