Angiotensin II-induced osteopontin expression in vascular smooth muscle cells involves Gq/11, Ras, ERK, Src and Ets-1

Hypertension Research : Official Journal of the Japanese Society of Hypertension
Keiko AbeTakafumi Ishida

Abstract

Recent studies suggest that osteopontin (OPN) plays a critical role in the progression of atherosclerotic plaques and that angiotensin II (Ang II) is a potent upregulator of OPN expression. The goal of the present study was to characterize the signaling mechanisms whereby Ang II increases OPN expression in vascular smooth muscle cells (VSMC). YM-254890, a specific inhibitor of G(q/11), potently suppressed Ang II-induced OPN expression and ERK1/2 activation. Among dominant-negative (DN) mutants of small G proteins, only DN-Ras suppressed Ang II-induced OPN promoter activity. DN-MEK1 markedly inhibited Ang II-induced OPN promoter activity, while neither DN-JNK nor DN-p38 MAP kinase had any effect. DN-Src and DN-Fyn suppressed Ang II-induced OPN promoter activity. YM-254890 inhibited Ang II-induced Src and Ras activation, and PP2, a selective inhibitor for the Src kinase family, inhibited Ras activation, suggesting that the G(q/11)-Src-Ras axis is the upstream signaling cascade for Ang II-induced OPN expression. Finally, small interfering RNA against Ets-1 suppressed Ang II-induced OPN expression. In conclusion, these data suggest that Ang II-induced OPN expression in VSMC is mediated by signaling cascades involving G(q/11) the Ra...Continue Reading

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Citations

Jun 27, 2009·Journal of Atherosclerosis and Thrombosis·Nwe Nwe SoeMasao Yoshizumi
Jan 21, 2016·Expert Opinion on Therapeutic Targets·Lucie HénautAlberto Ortiz
Feb 2, 2016·Biochemical and Biophysical Research Communications·Yulong DingHongyan Diao
Feb 26, 2014·BMC Systems Biology·Yuanzhe Bei, Pengyu Hong
Jul 29, 2011·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Hiroyuki NakayamaYasushi Fujio
Aug 5, 2011·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Arihiro KiyosueYasunobu Hirata
Jan 20, 2012·American Journal of Hypertension·Christian KrebsUlrich O Wenzel
Nov 20, 2013·The Journal of Biological Chemistry·Alicia N LyleW Robert Taylor
Oct 7, 2018·Laboratory Investigation; a Journal of Technical Methods and Pathology·Holly C WilliamsAlejandra San Martín
Feb 8, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Zoe Shin Yee Lok, Alicia N Lyle

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