VEGF Maintains Maternal Vascular Space Homeostasis in the Mouse Placenta through Modulation of Trophoblast Giant Cell Functions.
VEGF Maintains Maternal Vascular Space Homeostasis in the Mouse Placenta through Modulation of Trophoblast Giant Cell Functions.
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DOI：
10.3390/biom11071062
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发表时间：
2021-07-20
期刊：
影响因子：
5.5
通讯作者：
Nayak NR
中科院分区：
文献类型：
--
作者：
Fan X;Muruganandan S;Shallie PD;Dhal S;Petitt M;Nayak NR
血管内皮生长因子是一种血管生成生长因子，主要作用于内皮细胞，但大量研究表明，血管内皮生长因子也作用于非内皮细胞，包括滋养层细胞。通过在滋养层细胞中过量产生内源性可溶性血管内皮生长因子受体sFlt1而抑制血管内皮生长因子信号转导，已被认为与多种妊娠并发症有关。我们以前的研究和其他报道表明，血管内皮生长因子直接调节胎盘血管的发育和功能，过量的血管内皮生长因子的产生会对胎盘血管的发育产生不利影响。滋养层巨细胞(TGC)排列在小鼠胎盘血管的母体一侧，其功能类似内皮细胞。在这项研究中，我们使用了两个小鼠模型-子宫内膜血管内皮生长因子过度表达模型和胎盘特异性sFlt1基因敲除模型，专门研究了过量的血管内皮生长因子信号在与胎盘血管发育缺陷相关的TGC发育中的作用。胎龄11.5天和14.5天的子宫内膜血管内皮生长因子过表达母鼠胎盘在交界区的静脉母体间隙显著增大。排列在胎盘静脉间隙中的顶端TGC的大小和数量也显著增加。尽管在E17.5，对照组和高表达VEGF组的交界区静脉血间隙大小无明显差异，但高表达组胎盘P-TGC的数量和大小均显著增加。然而，在sFlt1基因敲除的胎盘中，迷路中正弦TGC排列的、碱性磷酸酶阳性的母体血液空间显著增加。这些结果提示，血管内皮生长因子信号通过调节胎盘TGC的发育和分化，在维持胎盘母体血管空间的动态平衡中发挥重要作用，这与血管内皮生长因子对其他血管床内皮细胞的作用类似。
Vascular endothelial growth factor (VEGF) is an angiogenic growth factor that acts primarily on endothelial cells, but numerous studies suggest that VEGF also acts on non-endothelial cells, including trophoblast cells. Inhibition of VEGF signaling by excess production of the endogenous soluble VEGF receptor sFlt1 in trophoblast cells has been implicated in several pregnancy complications. Our previous studies and other reports have shown that VEGF directly regulates placental vascular development and functions and that excess VEGF production adversely affects placental vascular development. Trophoblast giant cells (TGCs) line the maternal side of the placental vasculature in mice and function like endothelial cells. In this study, we specifically examined the effect of excess VEGF signaling on TGC development associated with defective placental vascular development using two mouse models an endometrial VEGF overexpression model and a placenta-specific sFlt1 knockdown model. Placentas of endometrial VEGF-overexpressing dams at embryonic days (E) 11.5 and 14.5 showed dramatic enlargement of the venous maternal spaces in junctional zones. The size and number of the parietal TGCs that line these venous spaces in the placenta were also significantly increased. Although junctional zone venous blood spaces from control and VEGF-overexpressing dams were not markedly different in size at E17.5, the number and size of P-TGCs were both significantly increased in the placentas from VEGF-overexpressing dams. In sFlt1 knockdown placentas, however, there was a significant increase in the size of the sinusoidal TGC-lined, alkaline phosphatase-positive maternal blood spaces in the labyrinth. These results suggest that VEGF signaling plays an important role in maintaining the homeostasis of the maternal vascular space in the mouse placenta through modulation of TGC development and differentiation, similar to the effect of VEGF on endothelial cells in other vascular beds.
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影响因子：
3.2
作者：
Furuya M;Kurasawa K;Nagahama K;Kawachi K;Nozawa A;Takahashi T;Aoki I
通讯作者：
Aoki I
影响因子：
4.6
作者：
Karaman, Sinem;Leppanen, Veli-Matti;Alitalo, Kari
通讯作者：
Alitalo, Kari
DOI：
10.1038/nrm3176
发表时间：
2011-08-23
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
2.7
作者：
Simmons, David G.;Fortier, Amanda L.;Cross, James C.
通讯作者：
Cross, James C.
影响因子：
0.7
作者：
Hu, Dong;Cross, James C.
通讯作者：
Cross, James C.