International Journal Of Bilogical Sciences
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ELK3 Suppresses Angiogenesis by Inhibiting the Transcriptional Activity of ETS-1 on MT1-MMP
Sun-Hee Heo and Je-Yoel Cho
Department of Veterinary Biochemistry, BK21 Plus, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea. Corresponding author: Je-Yoel Cho, D.V.M., Ph.D. Department of Veterinary Biochemistry, College of Veterinary Medicine, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea. Phone: +82-2-880-1268 Fax: +82-2-886-1268 E-mail: firstname.lastname@example.org
Ets transcription factors play important roles in vasculogenesis and angiogenesis. Knockout of the Ets gene family members in mice resulted in disrupted angiogenesis and malformed vascular systems. In this study, the role and mechanism of ELK3, an Ets factor, in angiogenesis was investigated using ELK3-specific siRNA in human vascular endothelial cells (HUVECs) and in vivo implantation assay. The suppression of ELK3 expression resulted in the reinforcement of VEGF-induced tube formation in HUVECs. The in vivo Matrigel plug assay also showed that ELK3 knockdown resulted in increased angiogenesis. Luciferase activity of the MT1-MMP promoter induced by ETS-1 factor was attenuated ELK3 co-transfection. CHIP assay showed the binding of ELK3 on the MT1-MMP promoter. MT1-MMP knockdown in the ELK3 knockdowned cells resulted in the decrease of tube formation suggesting that MT1-MMP transcriptional repression is required for ELK3-mediated anti-angiogenesis effect. Our data also showed that the suppressive effect of ELK3 on the angiogenesis was partly due to the inhibitory effect of ELK3 to the ETS-1 transcriptional activity on the MT1-MMP promoter rather than direct suppression of ELK3 on the target gene, since the expression level of co-repressor Sin3A is low in endothelial cells. Our results suggest that ELK3 plays a negative role of VEGF-induced angiogenesis through indirectly inhibiting ETS-1 function.
ELK3, VEGF, MT1-MMP, Sin3A.
Date Deposited : 09 Feb 2016 10:15
Official URL: http://www.ijbs.com/v10i4
Last Modified : 09 Feb 2016 10:15
Volume 10, Number 4, - 2014 , ISSN 1449-2288
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