uNK cell-derived TGF-β1 regulates the long noncoding RNA MEG3 to control vascular smooth muscle cell migration and apoptosis in spiral artery remodeling.

JOURNAL OF CELLULAR BIOCHEMISTRY(2019)

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摘要
Successful pregnancy depends on correct spiral artery (SpA) remodeling, and thus, on normal patterns of the vascular smooth muscle cell (VSMC) apoptosis and migration. Uterine natural killer (uNK) cells-derived transforming growth factor beta 1 (TGF-beta 1) is known to mediate the separation of VSMC layers via as yet unknown mechanisms. Likewise, the long noncoding RNA maternally expressed gene 3 (MEG3) is a tumor suppressor that has been shown to regulate cancer cell apoptosis and migration; however, its role in VSMC loss is unclear. Thus, the aim of the present study was to assess the effects of uNK-derived TGF-beta 1 and MEG3 on VSMC function during SpA. Analyses were conducted to assess the effects of downregulating MEG3 expression, and/or administering treatments to increase or block TGF-beta 1 signaling on VSMC survival and behavior. The results of these analyses showed that treating the VSMC with uNK cell-derived supernatant or recombinant human TGF-beta 1 promoted MEG3 and matrix metalloprotease 2 expression and VSMC apoptosis and migration, and suppressed VSMC proliferation. Conversely, MEG3 silencing promoted VSMC proliferation and inhibited VSMC apoptosis and migration. Notably, TGF-beta 1 signaling induction had no significant effect on the proliferation, apoptosis, nor migration of the MEG3-silenced VSMC. Together, these findings suggest that MEG3 is regulated by uNK-derived TGF-beta 1, and itself mediates VSMC apoptosis and migration; thus, it may be an important positive regulator of VSMCs separation during maternal SpA remodeling.
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关键词
long noncoding RNA maternally expressed gene 3,spiral artery remodeling,TGF-beta 1,uterine natural killer cell,vascular smooth muscle cell
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