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Fluid shear stress‐induced transcriptional activation of the vascular endothelial growth factor receptor‐2 gene requires Sp1‐dependent DNA binding
Author(s) -
Urbich Carmen,
Stein Monika,
Reisinger Kerstin,
Kaufmann Roland,
Dimmeler Stefanie,
Gille Jens
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)03879-6
Subject(s) - vascular endothelial growth factor b , vascular endothelial growth inhibitor , vascular endothelial growth factor , transcription factor , biology , endothelial stem cell , kinase insert domain receptor , vascular endothelial growth factor a , s1pr1 , receptor , microbiology and biotechnology , vascular endothelial growth factor c , sp1 transcription factor , downregulation and upregulation , gene expression , promoter , gene , cancer research , genetics , vegf receptors , in vitro
Hemodynamic forces play a fundamental role in the regulation of endothelial cell survival. As signaling via the vascular endothelial growth factor (VEGF) receptor‐2 pathway has been previously demonstrated to impact endothelial cell survival, we hypothesized that laminar shear stress may facilitate survival in part by inducing VEGF receptor‐2 expression. This study shows a time‐ and dose‐dependent upregulation of endothelial VEGF receptor‐2 expression by fluid shear stress in microvascular and large‐vessel derived endothelial cells. A functional analysis of the 5′‐regulatory region of the VEGF receptor‐2 promoter localized the shear stress‐response element to a sequence between bp −60 and −37 that encompasses two adjacent consensus Sp1 transcription factor binding sites. Constitutive and shear stress‐inducible Sp1‐dependent complexes are bound to this element, indicating that fluid shear stress‐induced transcriptional activation of the VEGF receptor‐2 gene requires Sp1‐dependent DNA binding. Together, these results suggest that biomechanical stimulation may lead to endothelial cell survival by upregulating VEGF receptor‐2 expression.