dNK derived IFN-γ mediates VSMC migration and apoptosis via the induction of LncRNA MEG3: A role in uterovascular transformation |
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| Institution: | 1. Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, United States;2. Center for Perinatal Studies, Swedish Medical Center, Seattle, WA, United States;3. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States;1. Embryo Implantation Laboratory, Hudson Institute, Clayton, VIC, Australia;2. Department of Molecular and Translational Medicine, Monash University, Clayton, VIC, Australia;3. Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia;1. Institute of Arthritis Research, 2220 East 25th St, Idaho Falls, ID 83404, USA;2. Idaho State University, Department of Biology, 921 South 8th Avenue, Pocatello, ID 83201, USA;1. Obstetrical Department, No.215 Hospital of Shanxi Nuclear Industry, Xianyang, Shaanxi, 712000, China;2. Obstetrical Department, Yan''an University Affiliated Hospital, Yan''an, Shaanxi, 716000, China;3. The 2nd Department of Obstetrical, Northwest Women and Children''s Hospital, Xian, Shaanxi, 710000, China;4. Obstetrical Department, Northwest Women and Children''s Hospital, Xian, Shaanxi, 710000, China;5. Gynaecology and Obstetrics, 4th (Xing Yuan) Hospital of Yulin, Yulin, Shaanxi, 719000, China;6. Gynaecology and Obstetrics, Xian NO.1 Hospital, Xian, Shaanxi, 710000, China;7. Obstetrical Department, Shaanxi Baoji Maternal and Child Health Hospital, Baoji 721000, China;8. Obstetrical Department, Yan''an People''s Hospital, Yanan, Shaanxi, 716000, China |
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| Abstract: | IntroductionAppropriate spiral artery remodeling is critical for successful fetal development and pregnancy outcomes. The vascular smooth muscle cell (VSMC) loss and separation, involving cell apoptosis and migration, plays an important role in this process. Decidual natural killer cells (dNK)-derived interferon gamma (IFN-γ), a key regulator of uterine arterial remodeling, can facilitate separation of VSMC layers, however, the specific mechanisms of it action are unknown. Long non-coding RNA MEG3 functions as tumor suppressor by regulating apoptosis and migration. Moreover, IFN-γ has been shown to influence cell vitality through regulating MEG3 expression. However, the functional role of dNK derived IFN-γ and MEG3 on VSMC viability, as well as the relationship between IFN-γ and MEG3 in VSMCs, has not been completely elaborated.MethodsThe up-regulation strategies and reagent treatment were employed to detect the effects of MEG3 and dNK/IFN-γ on VSMC proliferation, apoptosis and migration. At the same time, MEG3, p53 and matrix metalloproteinase 2 (MMP-2) expressions were investigated.Results: dNK/IFN-γ treatment led to up-regulation of MEG3 expression in VSMCs. Both MEG3 over-expression and dNK/IFN-γ treatment inhibited VSMC proliferation, stimulated VSMC migration and resulted in a small but significant induction of VSMC apoptosis, as well as promoted p53 and MMP-2 expression in VSMCs.DiscussionMEG3 is regulated by dNK-derived IFN-γ and regulates VSMC migration and apoptosis. Therefore, it may be an important positive regulator in VSMC loss from the maternal uterine spiral arteries during vascular transformation. |
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| Keywords: | LncRNA MEG3 VSMC loss Spiral artery remodeling dNK IFN-γ |
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