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Expression profiling of ETS and MMP factors in VEGF‐activated endothelial cells
Author(s) -
Heo SunHee,
Choi YoungJin,
Ryoo HyunMo,
Cho JeYoel
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb222
Subject(s) - angiogenesis , matrix metalloproteinase , umbilical vein , matrigel , vascular endothelial growth factor , mapk/erk pathway , in vivo , chemistry , transcription factor , microbiology and biotechnology , vascular endothelial growth factor a , transfection , cancer research , in vitro , biology , vegf receptors , signal transduction , gene , biochemistry
In the process of angiogenesis, working of many transcription factors at the proper time is important to activate angiogenesis‐related genes. In this study, we searched for Ets transcription factor members and matrix metalloproteinases (MMPs) that respond to VEGF in endothelial cells. We first analyzed the expression of 27 human Ets factors and 15 human MMPs in VEGF‐treated human umbilical vein endothelial cells (HUVEC) using quantitative RT‐PCR. We found that ETV‐1, Fli‐1, ERG, MMP‐1, ‐3, ‐7, ‐8, ‐9, ‐10, ‐13, and ‐19 expression is up‐regulated more than 1.5‐fold in HUVEC after 2 hr of VEGF treatment. In addition, the expression of MMP‐10 induced by VEGF remained 2‐fold higher for 24 hr compared to non‐treated control. The elevation of MMP10 mRNA and protein levels was confirmed to be both time‐ and dosage‐dependent. In addition, MMP‐10 transcription was mediated by Ets‐1. The inhibition of PI3K and MAPK inhibited VEGF‐induced MMP‐10 expression. Furthermore, transfection of MMP‐10 siRNA inhibited VEGF‐induced migration and tube formation, and it also inhibited vessel formation in matrigel plugs in vivo. In conclusion, our study demonstrated induction of MMP‐10 by VEGF in HUVEC and supports an angiogenic role for MMP‐10 in response to VEGF stimulation in vitro and in vivo.