{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T02:03:41Z","timestamp":1768529021290,"version":"3.49.0"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,5]]},"abstract":"\n Objective:<\/jats:title>\n 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).<\/jats:p>\n <\/jats:sec>\n \n Background:<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n 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-\u03b2 signaling and rescues lung hypoplasia both in vitro and in vivo. Also, prenatal miR-200b therapy decreases the observed incidence of CDH.<\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>","DOI":"10.1097\/sla.0000000000002595","type":"journal-article","created":{"date-parts":[[2017,11,14]],"date-time":"2017-11-14T18:31:29Z","timestamp":1510684289000},"page":"979-987","source":"Crossref","is-referenced-by-count":62,"title":["Prenatal microRNA miR-200b Therapy Improves Nitrofen-induced Pulmonary Hypoplasia Associated With Congenital Diaphragmatic Hernia"],"prefix":"10.1097","volume":"269","author":[{"given":"Naghmeh","family":"Khoshgoo","sequence":"first","affiliation":[{"name":"Departments of Surgery, Division of Pediatric Surgery, Pediatrics & Child Health and Physiology & Pathophysiology (Adjunct), University of Manitoba and Children's Hospital Research Institute of Manitoba, Biology of Breathing Theme, Winnipeg, Manitoba, Canada"}]},{"given":"Ramin","family":"Kholdebarin","sequence":"additional","affiliation":[{"name":"Departments of Surgery, Division of Pediatric Surgery, Pediatrics & Child Health and Physiology & Pathophysiology (Adjunct), University of Manitoba and Children's Hospital Research Institute of Manitoba, Biology of Breathing Theme, Winnipeg, Manitoba, Canada"}]},{"given":"Patricia","family":"Pereira-Terra","sequence":"additional","affiliation":[{"name":"Departments of Surgery, Division of Pediatric Surgery, Pediatrics & Child Health and Physiology & Pathophysiology (Adjunct), University of Manitoba and Children's Hospital Research Institute of Manitoba, Biology of Breathing Theme, Winnipeg, Manitoba, Canada"},{"name":"Life and Health Sciences Research Institute\/3B's\u2014PT Government Associate Laboratory, Braga\/Guimar\u00e3es, Portugal"}]},{"given":"Thomas H.","family":"Mahood","sequence":"additional","affiliation":[{"name":"Departments of Surgery, Division of Pediatric Surgery, Pediatrics & Child Health and Physiology & Pathophysiology (Adjunct), University of Manitoba and Children's Hospital Research Institute of Manitoba, Biology of Breathing Theme, Winnipeg, Manitoba, Canada"}]},{"given":"Landon","family":"Falk","sequence":"additional","affiliation":[{"name":"Departments of Surgery, Division of Pediatric Surgery, Pediatrics & Child Health and Physiology & Pathophysiology (Adjunct), University of Manitoba and Children's Hospital Research Institute of Manitoba, Biology of Breathing Theme, Winnipeg, Manitoba, Canada"}]},{"given":"Chelsea A.","family":"Day","sequence":"additional","affiliation":[{"name":"Departments of Surgery, Division of Pediatric Surgery, Pediatrics & Child Health and Physiology & Pathophysiology (Adjunct), University of Manitoba and Children's Hospital Research Institute of Manitoba, Biology of Breathing Theme, Winnipeg, Manitoba, Canada"}]},{"given":"Barbara M.","family":"Iwasiow","sequence":"additional","affiliation":[{"name":"Departments of Surgery, Division of Pediatric Surgery, Pediatrics & Child Health and Physiology & Pathophysiology (Adjunct), University of Manitoba and Children's Hospital Research Institute of Manitoba, Biology of Breathing Theme, Winnipeg, Manitoba, Canada"}]},{"given":"Fuqin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Departments of Surgery, Division of Pediatric Surgery, Pediatrics & Child Health and Physiology & Pathophysiology (Adjunct), University of Manitoba and Children's Hospital Research Institute of Manitoba, Biology of Breathing Theme, Winnipeg, Manitoba, Canada"}]},{"given":"Drew","family":"Mulhall","sequence":"additional","affiliation":[{"name":"Departments of Surgery, Division of Pediatric Surgery, Pediatrics & Child Health and Physiology & Pathophysiology (Adjunct), University of Manitoba and Children's Hospital Research Institute of Manitoba, Biology of Breathing Theme, Winnipeg, Manitoba, Canada"}]},{"given":"Carly","family":"Fraser","sequence":"additional","affiliation":[{"name":"Departments of Surgery, Division of Pediatric Surgery, Pediatrics & Child Health and Physiology & Pathophysiology (Adjunct), University of Manitoba and Children's Hospital Research Institute of Manitoba, Biology of Breathing Theme, Winnipeg, Manitoba, Canada"}]},{"given":"Jorge","family":"Correia-Pinto","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute\/3B's\u2014PT Government Associate Laboratory, Braga\/Guimar\u00e3es, Portugal"},{"name":"Department of Pediatric Surgery, Hospital de Braga, Braga, Portugal."}]},{"given":"Richard","family":"Keijzer","sequence":"additional","affiliation":[{"name":"Departments of Surgery, Division of Pediatric Surgery, Pediatrics & Child Health and Physiology & Pathophysiology (Adjunct), University of Manitoba and Children's Hospital Research Institute of Manitoba, Biology of Breathing Theme, Winnipeg, Manitoba, Canada"}]}],"member":"276","reference":[{"key":"R1-20231021","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1002\/ppul.22553","article-title":"Developmental and genetic aspects 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