PMID- 29895936 OWN - NLM STAT- MEDLINE DCOM- 20191021 LR - 20191022 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 8 IP - 1 DP - 2018 Jun 12 TI - Int6/eIF3e Silencing Promotes Placenta Angiogenesis in a Rat Model of Pre-eclampsia. PG - 8944 LID - 10.1038/s41598-018-27296-2 [doi] LID - 8944 AB - We investigated whether stable eukaryotic translation initiation factor 3e/inter 6 (eIF-3e/Int6) RNA-silencing (siRNA-Int6) can ameliorate pre-eclampsia (PE) by promoting angiogenesis in an N-nitro-L-arginine methyl ester (L-NAME)-induced rat pre-eclampsia (PE) model. Twenty-four pregnant female Sprague-Dawley rats were allocated into 4 groups, including controls (Con) without any treatment, and 18 from gestational day (GD) 7 to GD17 L-NAME-treated rats, which were divided into stable siRNA-Int6 transfected (siRNA-Int6), negative vector control siRNA (NC-siRNA) and PE control (PE-Con) groups. All adenovirus siRNA transfections were performed on GD7 via intravenous tail injection. On GD0, GD11 and GD17, blood pressure, and on GD6 and GD17, protein estimations in 24 h urine samples were conducted. All animals were sacrificed on GD18. In the PE-Con group, placental Int6 was expressed to a significantly greater level than in the Con group, which was reversed by the application of siRNA-Int6. Blood pressure and proteinuria were significantly lower in the siRNA-Int6 group than in the PRE-Con group. As shown by CD31 and IB4 expression, placental micro-vascular density (MVD) was significantly higher in the siRNA-Int6 group than in the PE-Con and NC-siRNA groups, which has accompanied by enhanced trophoblast invasion. Int6 silencing alleviated the maternal clinical manifestations of pre-eclampsia and promoted placental angiogenesis in pregnant L-NAME-treated rats. FAU - Li, Qin AU - Li Q AD - Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, No. 128, Shenyang Road, Shanghai, 200090, China. liqinbm@163.com. FAU - Yao, Baolin AU - Yao B AD - Department of Obstetrics, Obstetrics and Gynecology Hospital of Fudan University, No. 128, Shenyang Road, Shanghai, 200090, China. FAU - Endler, Alexander AU - Endler A AD - Department of Molecular Medical Research, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan. AD - Shanghai BIOMED Science Technology Co., Ltd, Room 2804-06 Baishu Building No. 1230, Zhongshan Bei Yi Road, Shanghai, 200437, China. FAU - Chen, Li AU - Chen L AD - Department of Molecular Medical Research, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan. AD - Shanghai BIOMED Science Technology Co., Ltd, Room 2804-06 Baishu Building No. 1230, Zhongshan Bei Yi Road, Shanghai, 200437, China. FAU - Shibasaki, Futoshi AU - Shibasaki F AD - Department of Molecular Medical Research, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan. FAU - Cheng, Haidong AU - Cheng H AD - Department of Obstetrics, Obstetrics and Gynecology Hospital of Fudan University, No. 128, Shenyang Road, Shanghai, 200090, China. hdcheng_2003@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180612 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Eukaryotic Initiation Factor-3) RN - V55S2QJN2X (NG-Nitroarginine Methyl Ester) SB - IM MH - Animals MH - Blood Pressure/genetics/physiology MH - Disease Models, Animal MH - Eukaryotic Initiation Factor-3/*genetics/metabolism MH - Female MH - Humans MH - NG-Nitroarginine Methyl Ester MH - Neovascularization, Physiologic/*genetics/physiology MH - Placenta/*blood supply/metabolism MH - Pre-Eclampsia/chemically induced/*genetics/metabolism MH - Pregnancy MH - Proteinuria/genetics/metabolism MH - *RNA Interference MH - Rats, Sprague-Dawley PMC - PMC5997673 COIS- The authors declare no competing interests. EDAT- 2018/06/14 06:00 MHDA- 2019/10/23 06:00 PMCR- 2018/06/12 CRDT- 2018/06/14 06:00 PHST- 2016/06/24 00:00 [received] PHST- 2018/05/30 00:00 [accepted] PHST- 2018/06/14 06:00 [entrez] PHST- 2018/06/14 06:00 [pubmed] PHST- 2019/10/23 06:00 [medline] PHST- 2018/06/12 00:00 [pmc-release] AID - 10.1038/s41598-018-27296-2 [pii] AID - 27296 [pii] AID - 10.1038/s41598-018-27296-2 [doi] PST - epublish SO - Sci Rep. 2018 Jun 12;8(1):8944. doi: 10.1038/s41598-018-27296-2.