Fluid shear stress‐induced transcriptional activation of the vascular endothelial growth factor receptor‐2 gene requires Sp1‐dependent DNA binding

FEBS Letters

Urbich, Carmen²  Dimmeler, Stefanie²  Reisinger, Kerstin¹  Stein, Monika¹  Gille, Jens¹  Kaufmann, Roland¹ 

[1] Department of Dermatology, Klinikum der J. W. Goethe-Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany;Molecular Cardiology, Department of Internal Medicine IV, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany

关键词: Vascular endothelium;    Endothelial growth factor receptor;    Mechanical stress;    Transcription factor;    Promoter region;    EMSA;    electrophoretic mobility shift assay;    HDMEC;    human dermal microvascular endothelial cells;    HUVEC;    human umbilical vein endothelial cells;    Luc;    luciferase;    VEGF;    vascular endothelial growth factor;    VEGFR;    vascular endothelial growth factor receptor;   

DOI  :  10.1016/S0014-5793(02)03879-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown