M2 macrophage-derived G-CSF promotes trophoblasts EMT, invasion and migration via activating PI3K/Akt/Erk1/2 pathway to mediate normal pregnancy.
M2 macrophage-derived G-CSF promotes trophoblasts EMT, invasion and migration via activating PI3K/Akt/Erk1/2 pathway to mediate normal pregnancy.
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M2巨噬细胞源性G-CSF通过激活PI3K/Akt/Erk1/2通路促进滋养层细胞EMT、侵袭和迁移介导正常妊娠
DOI：
10.1111/jcmm.16191
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发表时间：
2021-03
影响因子：
5.3
通讯作者：
Yang J
中科院分区：
文献类型：
--
作者：
Ding J;Yang C;Zhang Y;Wang J;Zhang S;Guo D;Yin T;Yang J
滋养细胞是胎盘的重要组成部分，在母胎串扰中起着至关重要的作用，充分的滋养细胞迁移和侵袭对胚胎着床和正常妊娠至关重要。巨噬细胞作为母体-胎儿界面个体微环境的主要组成部分，可与滋养细胞相互作用，参与正常妊娠的调控。之前，我们的团队已经证明滋养细胞可以通过分泌白细胞介素- 6 （IL - 6）诱导巨噬细胞向M2亚型极化；然而，对巨噬细胞调控滋养细胞迁移和侵袭的认识有限。在本研究中，我们采用共培养模型进一步研究巨噬细胞对滋养细胞迁移和侵袭的影响。我们的研究结果表明，与巨噬细胞共培养促进了滋养细胞的上皮向间充质转化（EMT），从而增强了它们的迁移和侵袭能力。进一步的实验表明，M2巨噬细胞衍生的G - CSF是通过激活PI3K/Akt/Erk1/2信号通路促进滋养细胞EMT、迁移和侵袭的关键因子。临床结果显示，G‐CSF在正常妊娠患者胎盘绒毛组织中的表达高于复发性自然流产患者，且其表达水平与EMT标志物显著相关。综上所述，这些发现表明M2巨噬细胞在调节滋养层细胞EMT、迁移和侵袭中的重要作用，有助于对巨噬细胞和滋养层细胞之间的串扰在正常妊娠的建立和维持中的新认识。
Trophoblasts are important parts of the placenta and exert vital roles in the maternal‐foetal crosstalk, and sufficient trophoblasts migration and invasion is critical for embryo implantation and normal pregnancy. Macrophages, as the major components of decidual microenvironment at maternal‐foetal interface, can interact with trophoblasts to participate in the regulation of normal pregnancy. Previously, our group have demonstrated that trophoblasts could induce macrophages polarization to M2 subtype by secreting interleukin‐6 (IL‐6); however, the understanding of macrophages regulating the migration and invasion of trophoblasts is limited. In the present study, we used the co‐cultured model to further investigate the effects of macrophages on trophoblasts migration and invasion. Our results showed that co‐culture with macrophages promoted epithelial‐to‐mesenchymal transition (EMT) of trophoblasts, thereby enhancing their migrative and invasive abilities. Further experiments revealed that M2 macrophage‐derived G‐CSF was a key factor, which promoted the EMT, migration and invasion of trophoblasts via activating PI3K/Akt/Erk1/2 signalling pathway. Clinically, G‐CSF was highly expressed in placental villous tissues of normal pregnancy patients compared to patients with recurrent spontaneous abortion, and its expression level was significantly correlation with EMT markers. Taken together, these findings indicate the important role of M2 macrophages in regulating trophoblasts EMT, migration and invasion, contributing to a new insight in concerning the crosstalk between macrophages and trophoblasts in the establishment and maintenance of normal pregnancy.
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影响因子：
7.8
作者：
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通讯作者：
Sedlmayr, P.
影响因子：
3.6
作者：
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通讯作者：
Illsley, Nicholas P.
影响因子：
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作者：
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通讯作者：
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