Activator protein-1 mediates shear stress-induced prostaglandin D synthase gene expression in vascular endothelial cells

Megumi Miyagi, Yoshikazu Miwa, Fumi Takahashi-Yanaga, Sachio Morimoto, Toshiyuki Sasaguri

研究成果: Contribution to journalArticle査読

33 被引用数 (Scopus)

抄録

Objective - We attempted to determine the molecular mechanism of fluid shear stress-induced lipocalin-type prostaglandin D synthase (L-PGDS) expression in vascular endothelial cells. Methods and Results - We examined the promoter region of the L-PGDS gene by loading laminar shear stress (20 dyne/cm 2), using a parallel-plate flow chamber, on endothelial cells transfected with luciferase reporter vectors containing the 5′-flanking regions of the human L-PGDS gene. A deletion mutant analysis revealed that a shear stress-responsive element resided in the region between -2607 and -2523 bp. A mutation introduced into the putative binding site for activator protein-1 (AP-1) within this region eliminated the response to shear stress. In an electrophoretic mobility shift assay, shear stress stimulated nuclear protein binding to the AP-1 binding site, which was supershifted by antibodies to c-Fos and c-Jun. Shear stress elevated the c-Jun phosphorylation level in a time-dependent manner, similar to that of L-PGDS gene expression. SP600125, a c-Jun N-terminal kinase inhibitor, decreased the c-Jun phosphorylation, DNA binding of AP-1, and L-PGDS expression induced by shear stress. Additionally, an mRNA chase experiment using actinomycin D demonstrated that shear stress did not stabilize L-PGDS mRNA. Conclusions - Shear stress induces L-PGDS expression by transcriptional activation through the AP-1 binding site.

本文言語英語
ページ(範囲)970-975
ページ数6
ジャーナルArteriosclerosis, thrombosis, and vascular biology
25
5
DOI
出版ステータス出版済み - 5 2005

All Science Journal Classification (ASJC) codes

  • 循環器および心血管医学

フィンガープリント

「Activator protein-1 mediates shear stress-induced prostaglandin D synthase gene expression in vascular endothelial cells」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル