dNK derived IFN-γ mediates VSMC migration and apoptosis via the induction of LncRNA MEG3: A role in uterovascular transformation

Introduction: Appropriate 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-gamma), 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-gamma has been shown to influence cell vitality through regulating MEG3 expression. However, the functional role of dNK derived IFN-gamma and MEG3 on VSMC viability, as well as the relationship between IFN-gamma and MEG3 in VSMCs, has not been completely elaborated. Methods: The up-regulation strategies and reagent treatment were employed to detect the effects of MEG3 and dNK/IFN-gamma on VSMC proliferation, apoptosis and migration. At the same time, MEG3, p53 and matrix metalloproteinase 2 (MMP-2) expressions were investigated. Results: dNK/IFN-gamma treatment led to up-regulation of MEG3 expression in VSMCs. Both MEG3 over expression and dNK/IFN-gamma 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. Discussion: MEG3 is regulated by dNK-derived IFN-gamma 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. (C) 2016 Elsevier Ltd. All rights reserved.