Aldosterone increases osteopontin gene expression in rat endothelial cells

Sugiyama, Toru; Yoshimoto, Takanobu; Hirono, Yuki; Suzuki, Noriko; Sakurada, Maya; Tsuchiya, Kyoichiro; Minami, Isao; Iwashima, Fumiko; Sakai, Haruna; Tateno, Toshitake; Sakakibara, Ryuji; Hirata, Yukio

doi:10.1016/j.bbrc.2005.08.056

Cited by 32 publications

(28 citation statements)

References 24 publications

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“…28,29 In this study, OPN gene transcription activity was enhanced dose-dependently and timedependently in Aldo-stimulated rVSMCs, which is consistent with reports in other various cell species, such as renal mesangium cells, 19 renal fibroblasts 21 and vascular endothelial cells. 30 As the basal levels of Aldo in the plasma of humans are around 3Â10 À10 M, a significant increase in OPN transcription starting at a concentration of 10 À9 M, as was observed in this in vitro analysis, seems to be within the clinical plasma Aldo fluctuation range.…”

Section: Discussionsupporting

confidence: 73%

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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Section: Discussionsupporting

confidence: 73%

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

et al. 2011

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“…A series of recent studies further revealed that increased expression of pro-inflammatory genes, such as VCAM-1, COX-2, and osteopontin, are preceded by 'aldosterone-induced vasculitis' [30,36,70]. We have also demonstrated that physiological concentrations of aldosterone (as low as 10 -10 M) directly acts on endothelial cells to induce osteopontin gene expression through the non-epithelial MR activation [71]. Since these inflammatory responses have been shown to be substantially abolished by treatment with MR antagonist independent of lowering blood pressure, it is assumable that MR activation in cardiovascular tissue plays a critical role in the initiation and the development of vascular inflammatory response.…”

Section: Mr Activation and Cardiovascular Injurymentioning

confidence: 67%

Aldosterone as a Cardiovascular Risk Hormone

Yoshimoto

Hirata

2007

Endocr J

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Abstract. The pathophysiological role of aldosterone in the development of cardiovascular disease has long been considered to be due its potent volume expansion/hypertensive effect mainly via mineralocorticoid receptor (MR) expressed in renal tubular epithelial cells. However, recent accumulating lines of evidence from clinical and experimental studies have suggested that direct cardiovascular effect of aldosterone contributes to the development of cardiovascular injury via MRs in non-epithelial tissue. A series of recent clinical studies have revealed that patients with primary aldosteronism have higher incidence of cardiovascular and renal complications than those with essential hypertension, and that aldosterone antagonism has cardiovascular protective effect in patients with heart failure independent from blood pressure. Numerous experimental studies have shown that both inflammation and oxidative stress play an initial and key role in the development of aldosterone-induced cardiovascular injury via non-epithelial MR activation. In this review, we discuss recent research progress in aldosterone and MR effects, with special emphasis on the pathophysiological role of aldosterone in cardiovascular diseases and the possible molecular mechanism(s) of cardiovascular injury by non-epithelial MR activation.

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“…4,5,12 Aldosterone is a steroid hormone that binds to the MR, a ligand-activated transcription factor. Steroid hormone receptors bind to specific DNA sequences in the promoters of hormone-responsive genes and recruit cofactors in a ligand-dependent manner, thereby modulating gene expression.…”

Section: Discussionmentioning

confidence: 99%

“…An animal model of hypertension caused by aldosterone and salt overload exhibits renal injury with increasing proinflammatory cytokines including OPN. 4 Aldosterone directly acts on the MR of endothelial cells to induce OPN gene expression 5 and it is therefore of interest that we have recently reported the independent association of plasma OPN levels with serum aldosterone levels in patients with essential hypertension. 6 In addition, plasma OPN levels were higher in patients with primary aldosteronism than with essential hypertension.…”

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confidence: 99%

Osteopontin in Rat Renal Fibroblasts

et al. 2008

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Abstract-Osteopontin (OPN), a proinflammatory cytokine, plays an important role in renal fibrosis. We reported that plasma OPN levels were higher in patients with primary aldosteronism than with essential hypertension. However, the regulatory mechanism of OPN by aldosterone remains unclear. Here, we report the transcriptional regulation of OPN expression by aldosterone and the functional effects of aldosterone-mediated OPN transcription in renal fibroblasts. Aldosterone induced OPN expression in a dose-dependent manner with significant responses at 10 nmol/L (1.6Ϯ0. OPN expression is induced by many growth factors and cytokines such as angiotensin II, basic fibroblast growth factor, 3 and aldosterone. Aldosterone binds to the mineralocorticoid receptor (MR) and plays an important role in the pathophysiology of renal disease. An animal model of hypertension caused by aldosterone and salt overload exhibits renal injury with increasing proinflammatory cytokines including OPN. 4 Aldosterone directly acts on the MR of endothelial cells to induce OPN gene expression 5 and it is therefore of interest that we have recently reported the independent association of plasma OPN levels with serum aldosterone levels in patients with essential hypertension. 6 In addition, plasma OPN levels were higher in patients with primary aldosteronism than with essential hypertension. 7 One of the direct actions of aldosterone may be the induction of systemic fibrosis by increasing proinflammatory cytokines including OPN.Previous studies have shown that various inducers regulate OPN expression at the transcriptional level with transcription factors such as Sp-1, 8 activator protein 1 (AP-1), 9,10 and nuclear factor kappa B (NFB). 10 However, the transcriptional regulatory mechanism of OPN by aldosterone remains unclear. In the present study, we demonstrated that aldosterone induces the transcription of the OPN gene through AP-1 and NFB via MR and plays an important role in renal fibrosis via OPN induction.

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Aldosterone increases osteopontin gene expression in rat endothelial cells

Cited by 32 publications

References 24 publications

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

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

Aldosterone as a Cardiovascular Risk Hormone

Osteopontin in Rat Renal Fibroblasts

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