PMID- 29932217 OWN - NLM STAT- MEDLINE DCOM- 20190408 LR - 20190408 IS - 1097-0223 (Electronic) IS - 0197-3851 (Linking) VI - 38 IP - 9 DP - 2018 Aug TI - MicroRNA 200b is upregulated in the lungs of fetal rabbits with surgically induced diaphragmatic hernia. PG - 645-653 LID - 10.1002/pd.5318 [doi] AB - OBJECTIVE: Profiling of miR-200b expression and its targets (transforming growth factor [TGF]-beta2 and ZEB2) in the surgical rabbit congenital diaphragmatic hernia (DH) model before and after tracheal occlusion (TO). METHODS: Thirty-eight timed-pregnant rabbits had left DH creation on gestational day (GD) 23. On GD28, 17 randomly selected fetuses had TO. We harvested fetuses at GD23, GD28, or GD30. We calculated lung-to-body weight ratios, processed lungs for miR-200b in situ hybridization and real-time quantitative polymerase chain reaction, and evaluated effects on downstream targets TGF-beta2 or ZEB2. RESULTS: We obtained 16 DH fetuses (n = 7 GD28 and n = 9 GD30), 13 TO fetuses (GD30), and 38 control fetuses (n = 15 GD23, n = 11 GD28, and n = 12 GD30). Diaphragmatic hernia lungs were hypoplastic, and TO resulted in control lung-to-body weight ratio levels. Term miR-200b-3p levels were significantly upregulated in the hypoplastic compared with control ipsilateral lung (1.906 +/- 0.90 vs 0.7429 +/- 0.44) (P < .01). Fetal TO ipsilateral lungs displayed a variable miR-200b response on in situ hybridization and polymerase chain reaction, with levels similar to control and congenital DH lungs. The TGF-beta2 was unchanged in hypoplastic and TO lungs, and ZEB2 tended to be reduced in TO compared with DH lungs (1.79 [0.4-2.9] vs 0.73 [0.5-1.4]). CONCLUSIONS: Hypoplastic fetal rabbit lungs display upregulation of miR-200b expression although downstream targets are not different from controls. Following TO, fetal rabbit lungs display a variable miR-200b response. CI - (c) 2018 John Wiley & Sons, Ltd. FAU - Eastwood, Mary Patrice AU - Eastwood MP AUID- ORCID: 0000-0002-6437-8972 AD - Cluster Organ Systems, Department of Development and Regeneration, and Center for Surgical Technologies, Group Biomedical Sciences, KU Leuven, Leuven, Belgium. FAU - Deprest, Jan AU - Deprest J AD - Cluster Organ Systems, Department of Development and Regeneration, and Center for Surgical Technologies, Group Biomedical Sciences, KU Leuven, Leuven, Belgium. AD - Fetal Medicine Unit, Clinical Department of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven, Belgium. AD - Research Department of Maternal Fetal Medicine, Institute for Women's Health (IWH), University College London, London, UK. FAU - Russo, Francesca Maria AU - Russo FM AUID- ORCID: 0000-0002-5029-7899 AD - Cluster Organ Systems, Department of Development and Regeneration, and Center for Surgical Technologies, Group Biomedical Sciences, KU Leuven, Leuven, Belgium. AD - Fetal Medicine Unit, Clinical Department of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven, Belgium. FAU - Wang, Hongmei AU - Wang H AD - Cluster Organ Systems, Department of Development and Regeneration, and Center for Surgical Technologies, Group Biomedical Sciences, KU Leuven, Leuven, Belgium. FAU - Mulhall, Drew AU - Mulhall D AD - Department of Surgery, Pediatrics & Child Health, University of Manitoba, Winnipeg, MB, Canada. AD - Department of Physiology, University of Manitoba, Winnipeg, MB, Canada. AD - Biology of Breathing, Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada. FAU - Iwasiow, Barbara AU - Iwasiow B AD - Department of Surgery, Pediatrics & Child Health, University of Manitoba, Winnipeg, MB, Canada. AD - Department of Physiology, University of Manitoba, Winnipeg, MB, Canada. AD - Biology of Breathing, Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada. FAU - Mahood, Thomas H AU - Mahood TH AD - Department of Surgery, Pediatrics & Child Health, University of Manitoba, Winnipeg, MB, Canada. AD - Department of Physiology, University of Manitoba, Winnipeg, MB, Canada. AD - Biology of Breathing, Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada. FAU - Keijzer, Richard AU - Keijzer R AUID- ORCID: 0000-0002-0108-3157 AD - Department of Surgery, Pediatrics & Child Health, University of Manitoba, Winnipeg, MB, Canada. AD - Department of Physiology, University of Manitoba, Winnipeg, MB, Canada. AD - Biology of Breathing, Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180717 PL - England TA - Prenat Diagn JT - Prenatal diagnosis JID - 8106540 RN - 0 (MicroRNAs) SB - IM MH - Animals MH - Disease Models, Animal MH - Female MH - Fetal Weight MH - Gestational Age MH - Hernias, Diaphragmatic, Congenital/etiology/*metabolism MH - In Situ Hybridization/veterinary MH - Lung/*chemistry/*embryology/metabolism MH - MicroRNAs/*analysis/genetics MH - Organ Size MH - Pregnancy MH - Rabbits MH - Real-Time Polymerase Chain Reaction/veterinary MH - Trachea/surgery MH - Up-Regulation EDAT- 2018/06/23 06:00 MHDA- 2019/04/09 06:00 CRDT- 2018/06/23 06:00 PHST- 2018/02/13 00:00 [received] PHST- 2018/06/13 00:00 [revised] PHST- 2018/06/14 00:00 [accepted] PHST- 2018/06/23 06:00 [pubmed] PHST- 2019/04/09 06:00 [medline] PHST- 2018/06/23 06:00 [entrez] AID - 10.1002/pd.5318 [doi] PST - ppublish SO - Prenat Diagn. 2018 Aug;38(9):645-653. doi: 10.1002/pd.5318. Epub 2018 Jul 17.