Ets family members induce lymphangiogenesis through physical and functional interaction with Prox1
| Autor: | Jun-ichi Suehiro, Tatsuhiko Kodama, Taichi Itoh, Tomoko Yamazaki, Masato Morikawa, Caname Iwata, Yasuyuki Morishita, Hajime Mihira, Kaori Harada, Tetsuro Watabe, Takashi Minami, Keiko Yuki, Kohei Miyazono, Yasuhiro Yoshimatsu |
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| Rok vydání: | 2011 |
| Předmět: |
Chromatin Immunoprecipitation
Angiogenesis Mutant Peritonitis Biology Proto-Oncogene Protein c-ets-2 Proto-Oncogene Protein c-ets-1 Mice Animals Humans Lymphangiogenesis RNA Small Interfering Cells Cultured Homeodomain Proteins Inflammation Mice Inbred BALB C Tumor Suppressor Proteins Endothelial Cells Gene Expression Regulation Developmental Cell Biology Vascular Endothelial Growth Factor Receptor-3 Embryonic stem cell Cell biology Chromatin Endothelial stem cell Lymphatic system Vascular endothelial growth factor C Thioglycolates Mutation Immunology |
| Zdroj: | Journal of Cell Science. 124:2753-2762 |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.083998 |
| Popis: | Prox1 plays pivotal roles during embryonic lymphatic development and maintenance of adult lymphatic systems by modulating the expression of various lymphatic endothelial cell (LEC) markers, such as vascular endothelial growth factor receptor 3 (VEGFR3). However, the molecular mechanisms by which Prox1 transactivates its target genes remain largely unknown. Here, we identified Ets-2 as a candidate molecule that regulates the functions of Prox1. Whereas Ets-2 has been implicated in angiogenesis, its roles during lymphangiogenesis have not yet been elucidated. We found that endogenous Ets-2 interacts with Prox1 in LECs. Using an in vivo model of chronic aseptic peritonitis, we found that Ets-2 enhanced inflammatory lymphangiogenesis, whereas a dominant-negative mutant of Ets-1 suppressed it. Ets-2 also enhanced endothelial migration towards VEGF-C through induction of expression of VEGFR3 in collaboration with Prox1. Furthermore, we found that both Prox1 and Ets-2 bind to the VEGFR3 promoter in intact chromatin. These findings suggest that Ets family members function as transcriptional cofactors that enhance Prox1-induced lymphangiogenesis. |
| Databáze: | OpenAIRE |
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