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

详细信息    查看全文

• 作者：Urbich ; Carmen ; Stein ; Monika ; Reisinger ; Kerstin ; Kaufmann ; Roland ; Dimmeler ; Stefanie ; Gille ; Jens
• 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 ce
• 刊名：FEBS Letters
• 出版年：2003
• 出版时间：January 30, 2003
• 年：2003
• 卷：535
• 期：1-3
• 页码：87-93
• 全文大小：192 K

文摘

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.