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Publication : Prox1 induces lymphatic endothelial differentiation via integrin alpha9 and other signaling cascades.

First Author  Mishima K Year  2007
Journal  Mol Biol Cell Volume  18
Issue  4 Pages  1421-9
PubMed ID  17287396 Mgi Jnum  J:124020
Mgi Id  MGI:3720405 Doi  10.1091/mbc.E06-09-0780
Citation  Mishima K, et al. (2007) Prox1 induces lymphatic endothelial differentiation via integrin alpha9 and other signaling cascades. Mol Biol Cell 18(4):1421-9
abstractText  During embryonic lymphatic development, a homeobox transcription factor Prox1 plays important roles in sprouting and migration of a subpopulation of blood vessel endothelial cells (BECs) toward VEGF-C-expressing cells. However, effects of Prox1 on endothelial cellular behavior remain to be elucidated. Here, we show that Prox1, via induction of integrin alpha9 expression, inhibits sheet formation and stimulates motility of endothelial cells. Prox1-expressing BECs preferentially migrated toward VEGF-C via up-regulation of the expression of integrin alpha9 and VEGF receptor 3 (VEGFR3). In mouse embryos, expression of VEGFR3 and integrin alpha9 is increased in Prox1-expressing lymphatic endothelial cells (LECs) compared with BECs. Knockdown of Prox1 expression in human LECs led to decrease in the expression of integrin alpha9 and VEGFR3, resulting in the decreased chemotaxes toward VEGF-C. These findings suggest that Prox1 plays important roles in conferring and maintaining the characteristics of LECs by modulating multiple signaling cascades and that integrin alpha9 may function as a key regulator of lymphangiogenesis acting downstream of Prox1.
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