Angiotensin II-Induced Osteopontin Expression in Vascular Smooth Muscle Cells Involves Gq/11, Ras, ERK, Src and Ets-1

Abe, Keiko; Nakashima, Hisashi; Ishida, Mari; Miho, Narimasa; Sawano, Mariko; Soe, Nwe Nwe; Kurabayashi, Masahiko; Chayama, Kazuaki; Yoshizumi, Masao; Ishida, Takafumi

doi:10.1291/hypres.31.987

Cited by 30 publications

(26 citation statements)

References 47 publications

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“…Although we did not show evidence that Pyk2 is a direct target of nifedipine, these data suggest that modulation of this Ca 2 -dependent kinase may be a major mechanism (upstream of Src) by which nifedipine acts to inhibit VSMC migration. Indeed, we and other investigators have shown that Pyk2 is involved in Src activation in response to other stimuli 28,29) . Pyk2 has been also shown to be involved in trophic responses and signaling, such as protein synthesis and activation of ERK, Akt and P70 S6 kinase 30,31) .…”

Section: Discussionmentioning

confidence: 61%

Nifedipine Interferes with Migration of Vascular Smooth Muscle Cells via Inhibition of Pyk2-Src Axis

Soe

Ishida

Miho

et al. 2009

JAT

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Section: Discussionmentioning

confidence: 61%

Nifedipine Interferes with Migration of Vascular Smooth Muscle Cells via Inhibition of Pyk2-Src Axis

Soe

Ishida

Miho

et al. 2009

JAT

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“…[31][32][33][34] Although there are only a few reports on Aldo-induced OPN production, Irita et al 21 reported the involvement of activator protein-1 and nuclear factor-kB in the Aldo stimulation of rat renal fibroblasts. Contrary to these past investigations, our study revealed that the formation of an Aldo-MR complex and its binding to GRE were pivotal for the upregulation of OPN gene transcription.…”

Section: Discussionmentioning

confidence: 99%

Aldosterone-induced osteopontin gene transcription in vascular smooth muscle cells involves glucocorticoid response element

et al. 2011

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Osteopontin (OPN) is known to be one of the cytokines that is involved in the vascular inflammation caused by aldosterone (Aldo). Previous reports have shown that Aldo increases OPN transcripts, and the mechanisms for this remain to be clarified. In this study, we investigated how Aldo increases OPN transcripts in the vascular smooth muscle cells of rats. Aldosterone increased OPN transcripts time-dependently as well as dose-dependently. This increase was diminished by eplerenone, a mineralocorticoid receptor (MR) antagonist. Luciferase promoter assays showed that the OPN promoter deleted to the À1599 site retained the same promoting ability as the full-length OPN promoter when stimulated by 10 À7 M Aldo, but the promoter deleted to the À1300 site lost the promoting ability. A glucocorticoid response element (GRE) is located in that deleted region. Luciferase assays of a mutated promoter without the GRE lost the luciferase upregulation, although mutated promoters with the deletion of other consensus sites maintained the promoter activity. The binding of the Aldo-MR complex to the GRE fragment was confirmed by an electrophoretic-mobility shift assay. This is the first report showing that Aldo regulates the transcriptional levels of OPN and inflammatory responses in the vasculature through a specific GRE site in the OPN promoter region.

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“…In an in vitro study, Abe et al 18 reported that OPN expression induced by AII was blocked by valsartan in rat vascular smooth muscle cells. We also reported that aldosterone increased OPN and that the increase was abolished by the mineralocorticoid receptor antagonist, spironolactone, in renal fibroblast.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II receptor blockade with valsartan decreases plasma osteopontin levels in patients with essential hypertension

et al. 2010

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Osteopontin (OPN) has recently emerged as a key factor in both vascular remodelling and development of atherosclerosis. It has been reported that OPN is regulated by the renin-angiotensin-aldosterone system (RAAS). The aim of this study was to clarify the effect of angiotensin II receptor blockade with valsartan on plasma OPN levels in patients with essential hypertension (EHT). Forty-six patients (mean age, 64 ± 11 years) with EHT were randomly assigned to treatment with amlodipine or valsartan. There were no significant differences in baseline clinical characteristics between the two groups. Blood sampling and blood pressure evaluation were performed before and after 24 weeks of treatment. After 24 weeks, both systolic blood pressure (SBP) and diastolic blood pressure (DBP) were decreased significantly and by the same degree in each treatment group. However, valsartan but not amlodipine decreased plasma OPN levels (baseline and 24-week data-valsartan: 614±224 ng ml À1, 472±268 ng ml À1 , P ¼ 0.006; amlodipine: 680 ± 151 ng ml À1 , 687 ± 234 ng ml À1 , P40.999). A positive correlation between the reduction in OPN and the log natural (ln) C-reactive protein (CRP) was seen in the valsartan-treated group. Stepwise regression analysis showed that treatment with valsartan and the reduction of ln CRP were associated with the reduction in OPN levels, and this association was independent of the reduction in SBP or aldosterone levels (valsartan: b ¼ 0.332, P ¼ 0.026; ln CRP reduction: b ¼ 0.366, P ¼ 0.015). These results suggest that suppression of the RAAS and inflammation may decrease plasma OPN levels.

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Angiotensin II-Induced Osteopontin Expression in Vascular Smooth Muscle Cells Involves Gq/11, Ras, ERK, Src and Ets-1

Cited by 30 publications

References 47 publications

Nifedipine Interferes with Migration of Vascular Smooth Muscle Cells via Inhibition of Pyk2-Src Axis

Nifedipine Interferes with Migration of Vascular Smooth Muscle Cells via Inhibition of Pyk2-Src Axis

Aldosterone-induced osteopontin gene transcription in vascular smooth muscle cells involves glucocorticoid response element

Angiotensin II receptor blockade with valsartan decreases plasma osteopontin levels in patients with essential hypertension

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