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



The 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.



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.



MEG3 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.
Department of Obstetrics and Gynecology, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China.
Weifang
W
Liu
Department of Obstetrics and Gynecology, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China.
Xiaoxia
X
Liu
Department of Obstetrics and Gynecology, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China.
Minglian
M
Luo
Department of Obstetrics and Gynecology, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China.
Xiaoping
X
Liu
Department of Obstetrics and Gynecology, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China.
Qingqing
Q
Luo
Department of Obstetrics and Gynecology, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China.
Hui
H
Tao
Department of Obstetrics and Gynecology, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China.
Di
D
Wu
Department of Obstetrics and Gynecology, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China.
Sisi
S
Lu
Department of Obstetrics and Gynecology, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China.
Jing
J
Jin
Department of Obstetrics and Gynecology, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China.
Yin
Y
Zhao
Department of Obstetrics and Gynecology, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: xiehezouli@126.com.
Li
L
Zou
D001011:Aorta / Q000166:cytology / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D003656:Decidua / Q000166:cytology / Q000378:metabolism; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000378:metabolism; D015854:Up-Regulation
C498907:MEG3 non-coding RNA, human; D062085:RNA, Long Noncoding; D007371:Interferon-gamma; D020778:Matrix Metalloproteinase 2
IFN-γ; LncRNA MEG3; Spiral artery remodeling; VSMC loss; dNK