Induction of VEGF Gene Transcription by IL-1   is Mediated Through Stress-activated MAP Kinases and Sp1 Sites in Cardiac Myocytes

Tanaka, Toru; Kanai, Hiroyuki; Sekiguchi, Kenichi; Aihara, Yasushi; Yokoyama, Tetsuji; Arai, M.; Kanda, Tugiyasu; Nagai, Ryozo; Kurabayashi, Masahiko

doi:10.1006/jmcc.2000.1228

Cited by 105 publications

(78 citation statements)

References 37 publications

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“…There are many reports that Ang-II activates p38 MAPK in various kinds of cells including mesangial cells (Reddy et al 2002) and vascular smooth muscle cells (Touyz et al 2001). There is now a wealth of data supporting a direct role for p38 MAPK as a signaling pathway in the production of VEGF (Tanaka et al 2000, Jung et al 2001, Duyndam et al 2003, Tokuda et al 2003, Tsai et al 2003. Therefore, in this study, we focused on the p38 MAPK pathway to identify the signaling pathways that mediate Ang-II-induced VEGF synthesis.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II stimulates the synthesis of vascular endothelial growth factor through the p38 mitogen activated protein kinase pathway in cultured mouse podocytes

Kang¹,

Park²,

Kim³

et al. 2006

Journal of Molecular Endocrinology

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Section: Discussionmentioning

confidence: 99%

Angiotensin II stimulates the synthesis of vascular endothelial growth factor through the p38 mitogen activated protein kinase pathway in cultured mouse podocytes

Kang¹,

Park²,

Kim³

et al. 2006

Journal of Molecular Endocrinology

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“…Since the first description of the significance of the Sp1 site cluster in close proximity to the transcription start (Gille et al, 1997;Ryuto et al, 1996), this region has been implicated in the regulation of VEGF/VPF gene transcription in response to several important stimuli (Finkenzeller et al, 1997;Gille et al, 1998;Tanaka et al, 2000). Moreover, transrepression of VEGF/VPF promoter activity by von Hippel-Lindau and p53 tumor suppressor gene product was shown to be mediated via interaction with this GC-rich region (Mukhopadhyay et al, 1997;Zhang et al, 2000).…”

Section: Hgf/sf-induced Vegf/vpf Gene Expression Is Mediated Via Actimentioning

confidence: 99%

Increased Sp1 phosphorylation as a mechanism of hepatocyte growth factor (HGF/SF)-induced vascular endothelial growth factor (VEGF/VPF) transcription

Reisinger

Kaufmann

Gille

2003

Journal of Cell Science

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Hepatocyte growth factor (HGF/SF)-induced expression of vascular endothelial growth factor (VEGF/VPF) has been implicated in paracrine amplification of angiogenesis, contributing to angiogenic responses during inflammation, wound healing, collateral formation and tumor growth. We have shown previously that HGF/SF-mediated VEGF/VPF expression by keratinocytes is primarily dependent on transcriptional activation, and we mapped the HGF/SF-responsive element to a GC-rich region between bp -88 and -65. Sp1-like factors bind to this element constitutively; however the VEGF/VPF promoter is transactivated by HGF/SF in the absence of induced binding activity. In experimental approaches to clarify molecular mechanisms of Sp1-dependent VEGF/VPF gene transcription, neither HGF/SF-dependent changes in nuclear expression nor in relative DNA binding activity of Sp family members to the indicated element were observed. Thus, HGF/SF was hypothesized to induce VEGF/VPF gene transcription via increased transactivation activity of Sp1 owing to biochemical modification. In immunoprecipitation studies, HGF/SF was found to increase the amount of serine-phosphorylated Sp1, revealing a likely mechanism of HGF/SF-induced VEGF/VPF expression, as phosphorylation may enhance the transcriptional activity of Sp1. The contribution of different signaling molecules to HGF/SF-induced VEGF/VPF transcription was demonstrated by the use of chemical inhibition, of expression of kinase-deficient signaling proteins, and by the use of antisense oligonucleotides. Herein, we provide evidence that PI 3-kinase, MEK1/2 and PKC-ζ play a significant role in HGF/SF-induced VEGF/VPF promoter activation. Together, our results elucidate a critical pathway of paracrine amplification of angiogenesis, suggesting that HGF/SF-induced Sp1 phosphorylation may activate VEGF/VPF promoter activity that requires the contribution of distinct signaling molecules.

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“…The key regulator of VEGF expression is hypoxia (19,20); however, a range of cytokines and growth factors have been shown to regulate and correlate with VEGF expression. Interleukin (IL)1a/b stimulates production of VEGF in a diverse range of cell types, including human cultured synovial fibroblasts (21), peripheral blood mononuclear cells (22), vascular smooth muscle cells (23) and cardiac myocytes (24), and also in rat ovary cells (25). In parallel with this, another cytokine seen to regulate VEGF in a variety of tissues is IL6.…”

Section: Introductionmentioning

confidence: 99%

Correlation of VEGF production with IL1α and IL6 secretion by human pituitary adenoma cells

Borg

Kerry²,

Royds³

et al. 2005

eur j endocrinol

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Objectives: Vascular endothelial growth factor (VEGF) is considered to be the most important angiogenic factor involved in the neovascularisation of solid tumours. Regulatory molecules include cytokines and growth factors. Interleukin (IL)1 and IL6 have both been shown to regulate VEGF levels in a variety of tissues. The role of cytokines in the pathogenesis of pituitary tumours remains unclear. We have examined the expression of VEGF and its relationships with IL1 and IL6 in the human pituitary tumour cell line HP75 and a series of human pituitary tumours. We have also looked at the relationship of tumour volume and invasive status to VEGF secretion. Methods: Surgically resected tumours were routinely cultured in single-cell suspension at 200 K/well (standard unit for culture of dispersed primary pituitary adenoma cells). We measured VEGF, IL1a and IL6 levels by ELISA. Tumour volume and invasion grade were assessed by preoperative magnetic resonance imaging. Results: VEGF was detected in conditioned medium of HP75 cells (900^52 pg/ml) and in 82% of tumours tested (range 26-16 464 pg/ml). Tumour volume and secretion of VEGF were significantly associated with levels of IL6 (volume, P ¼ 0.056; VEGF, P , 0.001 (P values based on Spearman's test)) and IL1a produced (volume, P , 0.005; VEGF, P , 0.001). Invasive tumours showed a higher basal secretion of VEGF that that of the non-invasive type; however, this difference was not significant. Addition of exogenous IL1a, but not IL6, significantly increased VEGF production. Conclusions: The significant associations between VEGF and the levels of IL6 and IL1a suggest an important role for these cytokines in the development of these tumours.European Journal of Endocrinology 152 293-300

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Induction of VEGF Gene Transcription by IL-1 is Mediated Through Stress-activated MAP Kinases and Sp1 Sites in Cardiac Myocytes

Cited by 105 publications

References 37 publications

Angiotensin II stimulates the synthesis of vascular endothelial growth factor through the p38 mitogen activated protein kinase pathway in cultured mouse podocytes

Angiotensin II stimulates the synthesis of vascular endothelial growth factor through the p38 mitogen activated protein kinase pathway in cultured mouse podocytes

Increased Sp1 phosphorylation as a mechanism of hepatocyte growth factor (HGF/SF)-induced vascular endothelial growth factor (VEGF/VPF) transcription

Correlation of VEGF production with IL1α and IL6 secretion by human pituitary adenoma cells

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