RRC ID 45267
著者 Suenaga K, Kitahara S, Suzuki Y, Kobayashi M, Horie S, Sugawara J, Yaegashi N, Sato Y.
タイトル Role of the vasohibin family in the regulation of fetoplacental vascularization and syncytiotrophoblast formation.
ジャーナル PLoS One
Abstract 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.
巻・号 9(9)
ページ e104728
公開日 2014-1-1
DOI 10.1371/journal.pone.0104728
PII PONE-D-14-13881
PMID 25184477
PMC PMC4153575
MeSH Adenoviridae / genetics Adult Angiogenic Proteins / genetics* Angiogenic Proteins / metabolism Animals Cell Cycle Proteins / genetics* Cell Cycle Proteins / metabolism Cell Fusion Cell Line, Tumor Colforsin / pharmacology DNA-Binding Proteins Female Gene Expression Regulation Gene Products, env / genetics Gene Products, env / metabolism Genetic Vectors Humans Mice Mice, Inbred C57BL Mice, Knockout Neovascularization, Physiologic* Nuclear Proteins / genetics Nuclear Proteins / metabolism Pregnancy Pregnancy Proteins / genetics Pregnancy Proteins / metabolism Signal Transduction Transcription Factors / genetics Transcription Factors / metabolism Trophoblasts / cytology Trophoblasts / drug effects Trophoblasts / metabolism*
IF 2.74
引用数 10
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 BeWo