Prox1 Induces Lymphatic Endothelial Differentiation via Integrin α9 and Other Signaling Cascades
| Autor: | Kohei Miyazono, Tetsuro Watabe, Yuichi Oike, Akira Saito, Masanori Hirashima, Yasuhiro Yoshimatsu, Toshio Suda, Makoto Araie, Hajime Kubo, Natsuko Imaizumi, Koichi Mishima, Shinji Masui, Hitoshi Niwa, Tohru Morisada |
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| Rok vydání: | 2007 |
| Předmět: |
Vascular Endothelial Growth Factor A
Cellular differentiation Vascular Endothelial Growth Factor C Biology CD49c Cell Line Lymphatic System Mice Cell Movement Animals Humans Molecular Biology Transcription factor Embryonic Stem Cells Homeodomain Proteins Chemotaxis Tumor Suppressor Proteins Endothelial Cells Gene Expression Regulation Developmental Cell Differentiation Articles Cell Biology Vascular Endothelial Growth Factor Receptor-3 Cell biology Vascular endothelial growth factor A Lymphatic system Integrin alpha M Vascular endothelial growth factor C biology.protein Integrin beta 6 Endothelium Vascular Integrin alpha Chains Signal Transduction |
| Zdroj: | Molecular Biology of the Cell. 18:1421-1429 |
| ISSN: | 1939-4586 1059-1524 |
| DOI: | 10.1091/mbc.e06-09-0780 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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