キタハラ　シユウジ   Kitahara Shiyuuji   北原　秀治    所属   医学研究科 医学研究科 (医学部医学科をご参照ください)    職種   特任准教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Role of the vasohibin family in the regulation of fetoplacental vascularization and syncytiotrophoblast formation.
掲載誌名	正式名：PloS one 略　 称：PLoS One ISSNコード：(1932-6203)1932-6203(Linking)
掲載区分	国外
巻・号・頁	9(9),pp.e104728
著者・共著者	Suenaga Kaori, Kitahara Shuji, Suzuki Yasuhiro, Kobayashi Miho, Horie Sachiko, Sugawara Junichi, Yaegashi Nobuo, Sato Yasufumi
発行年月	2014
概要	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.
DOI	10.1371/journal.pone.0104728
PMID	25184477