Role of the vasohibin family in the regulation of fetoplacental vascularization and syncytiotrophoblast formation.
Role of the vasohibin family in the regulation of fetoplacental vascularization and syncytiotrophoblast formation.
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DOI：
10.1371/journal.pone.0104728
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Sato Y
中科院分区：
文献类型：
--
作者：
Suenaga K;Kitahara S;Suzuki Y;Kobayashi M;Horie S;Sugawara J;Yaegashi N;Sato Y
Vasohibin-1(VASH1)和Vasohibin-2(VASH2)是Vasohibin家族中的两个成员，已被确定为新的血管生成调节因子。VASH1阻止血管生成，而VASH2刺激萌芽。在这里，我们描述了它们在胎盘中的功能作用。人胎盘组织的免疫组织化学分析明确了它们的独特定位；VASH1位于内皮细胞，VASH2位于滋养层细胞。然后，我们用一个小鼠模型来探索它们的功能。以C57BL6为背景的野生型、Vash1(−/−)和Vash2(−/−)小鼠用于他们的第一次怀孕。正如预期的那样，与野生型相比，Vash1(−/−)小鼠的胎儿血管面积增加，而Vash2(−/−)小鼠的胎儿血管面积减少。此外，我们注意到，18.5dpc的Vash2(−/−)小鼠迷路绒毛较薄，母体陷窝较大。电子显微镜观察发现，Vash2(−/−)小鼠合体滋养层细胞的形成存在缺陷。为了测试VASH2可能参与合体滋养层细胞的形成，我们研究了人滋养细胞样绒癌细胞系BeWo细胞的融合。Forsklin处理可诱导BeWo细胞融合，VASH2表达下调明显抑制这种细胞融合。反之，携带人VASH2基因的腺病毒载体感染后，VASH2基因的过表达显著增加了BeWo细胞的融合。胶质细胞缺失-1和内源性逆转录病毒包膜糖蛋白Syncytin 1和Syncytin 2参与了滋养层细胞的融合。然而，VASH2没有改变它们在BeWo细胞中的表达。这些结果表明，VASH1和VASH2在胎儿胎盘血管形成中具有明显的定位和相反作用。此外，我们的研究首次表明，在滋养层细胞中表达的VASH2参与了合体滋养层细胞形成的细胞融合的调节。
Vasohibin-1 (VASH1) and vasohibin-2 (VASH2), the 2 members of the vasohibin family, have been identified as novel regulators of angiogenesis. VASH1 ceases angiogenesis, whereas VASH2 stimulates sprouting. Here we characterized their functional role in the placenta. Immunohistochemical analysis of human placental tissue clarified their distinctive localization; VASH1 in endothelial cells and VASH2 in trophoblasts. We then used a mouse model to explore their function. Wild-type, Vash1(−/−), and Vash2(−/−) mice on a C57BL6 background were used in their first pregnancy. As expected, the fetal vascular area was increased in the Vash1(−/−) mice, whereas it was decreased in the Vash2(−/−) mice relative to wild-type. In addition, we noticed that the Vash2(−/−) mice at 18.5dpc displayed thinner villi of the labyrinth and larger maternal lacunae. Careful observation by an electron microscopy revealed that the syncytiotrophoblast formation was defective in the Vash2(−/−) mice. To test the possible involvement of VASH2 in the syncytiotrophoblast formation, we examined the fusion of BeWo cells, a human trophoblastoid choriocarcinoma cell line. The forskolin treatment induced the fusion of BeWo cells, and the knockdown of VASH2 expression significantly inhibited this cell fusion. Conversely, the overexpression of VASH2 by the infection with adenovirus vector encoding human VASH2 gene significantly increased the fusion of BeWo cells. Glial cell missing-1 and endogenous retrovirus envelope glycoprotein Syncytin 1 and Syncytin 2 are known to be involved in the fusion of trophoblasts. However, VASH2 did not alter their expression in BeWo cells. These results indicate that VASH1 and VASH2 showed distinctive localization and opposing function on the fetoplacental vascularization. Moreover, our study shows for the first time that VASH2 expressed in trophoblasts is involved in the regulation of cell fusion for syncytiotrophoblast formation.
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影响因子：
5.7
作者：
Tamaki, Kentaro;Moriya, Takuya;Sasano, Hironobu
通讯作者：
Sasano, Hironobu
影响因子：
6
作者：
Hosaka, Tomoko;Kimura, Hiroshi;Sato, Yasufumi
通讯作者：
Sato, Yasufumi
影响因子：
16.6
作者：
Matsuura, Ken;Jigami, Takafumi;Akiyama, Tetsu
通讯作者：
Akiyama, Tetsu
影响因子：
3.6
作者：
Chen, Chie-Pein;Chen, Liang-Fu;Chen, Hungwen
通讯作者：
Chen, Hungwen
DOI：
10.1073/pnas.1112304108
发表时间：
2011-11-15
影响因子：
11.1
作者：
Dupressoir, Anne;Vernochet, Cecile;Heidmann, Thierry
通讯作者：
Heidmann, Thierry