Identification of targets of Prox1 during in vitro vascular differentiation from embryonic stem cells: Functional roles of HoxD8 in lymphangiogenesis

Kaori Harada, Tomoko Yamazaki, Caname Iwata, Yasuhiro Yoshimatsu, Hitoshi Sase, Koichi Mishima, Yasuyuki Morishita, Masanori Hirashima, Yuichi Oike, Toshio Suda, Naoyuki Miura, Tetsuro Watabe, Kohel Miyazono

研究成果: Article査読

25 被引用数 (Scopus)

抄録

During lymphatic development, Prox1 plays central roles in the differentiation of blood vascular endothelial cells (BECs) into lymphatic endothelial cells (LECs), and subsequently in the maturation and maintenance of lymphatic vessels. However, the molecular mechanisms by which Prox1 elicits these functions remain to be elucidated. Here, we identified FoxC2 and angiopoietin-2 (Ang2), which play important roles in the maturation of lymphatic vessels, as novel targets of Prox1 in mouse embryonic-stem-cell-derived endothelial cells (MESECs). Furthermore, we found that expression of HoxD8 was significantly induced by Prox1 in MESECs, a finding confirmed in human umbilical vein endothelial cells (HUVECs) and human dermal LECs (HDLECs). In mouse embryos, HoxD8 expression was significantly higher in LECs than in BECs. In a model of inflammatory lymphangiogenesis, diameters of lymphatic vessels of the diaphragm were increased by adenovirally transduced HoxD8. We also found that HoxD8 induces Ang2 expression in HDLECs and HUVECs. Moreover, we found that HoxD8 induces Prox1 expression in HUVECs and that knockdown of HoxD8 reduces this expression in HDLECs, suggesting that Prox1 expression in LECs is maintained by HoxD8. These findings indicate that transcriptional networks of Prox1 and HoxD8 play important roles in the maturation and maintenance of lymphatic vessels.

本文言語English
ページ(範囲)3923-3930
ページ数8
ジャーナルJournal of Cell Science
122
21
DOI
出版ステータスPublished - 2009

ASJC Scopus subject areas

  • 細胞生物学

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