Shear stress induces expression of vascular endothelial growth factor receptor Flk-1/KDR through the CT-rich Sp1 binding site

Takeo Abumiya, Toshiyuki Sasaguri, Yoji Taba, Yoshikazu Miwa, Megumi Miyagi

研究成果: ジャーナルへの寄稿学術誌査読

55 被引用数 (Scopus)

抄録

Fluid shear stress is 1 of the major factors that control gene expression in vascular endothelial cells. We investigated the role of shear stress in the regulation of the expression of fetal liver kinase-1/kinase domain region (Flk-1/KDR), a vascular endothelial growth factor receptor, by using human umbilical vein endothelial cells. Laminar shear stress (15 dyne/cm2) elevated Flk-1/KDR mRNA levels by ≈3-fold for 8 hours, and the expression was upregulated within the range of 5 to 40 dyne/cm2. Deletion analysis of the 5′-flanking region of the Flk-1/KDR gene promoter by use of a luciferase reporter vector revealed that a shear stress-responsive element resided in the sequence between -94 and -31 bp, which contained putative nuclear factor-κB, activator protein-2, and GC-rich Sp1 and CT-rich Sp1 binding sites. Electrophoretic mobility shift assay demonstrated that nuclear extract was bound to the GC-rich Sp1 sites and the CT-rich Sp1 site with a similar pattern. However, shear stress enhanced the DNA-protein interactions only on the CT-rich Sp1 site but not on the GC-rich Sp1 sites. A 3-bp mutation in the CT-rich Sp1 site eliminated the response to shear stress in electrophoretic mobility shift assay and luciferase reporter assay. These results suggest that shear stress induces Flk-1/KDR expression through the CT-rich Sp1 binding site.

本文言語英語
ページ(範囲)907-913
ページ数7
ジャーナルArteriosclerosis, thrombosis, and vascular biology
22
6
DOI
出版ステータス出版済み - 6月 29 2002
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 循環器および心血管医学

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