PGE2 Stimulates VEGF Expression in Endothelial Cells via ERK2/JNK1 Signaling Pathways

Pai, Rama; Szabó, Imre; Soreghan, Brian A.; Atay, Songul; Kawanaka, Hirofumi; Tarnawski, Andrzej S.

doi:10.1006/bbrc.2001.5494

Cited by 179 publications

(112 citation statements)

References 31 publications

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“…There is a possibility that endogenous PGE 2 may induce VEGF mRNA expression in luteal cells. Supporting our observations are reports that show a similar PGE 2 -mediated enhancement of VEGF expression in rat gastric microvascular endothelial cells (Pai et al 2001) and human + RNA (0·5 g RNA) was then extracted from the cultured cells for Northern blot analysis. The relative densities were determined by normalization against the G3PDH mRNA levels (triplicate wells in each case).…”

Section: Discussionsupporting

confidence: 87%

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Vascular endothelial growth factor increases messenger RNAs encoding cyclooxygenase-II and membrane-associated prostaglandin E synthase in rat luteal cells

Sakurai¹,

Tamura²,

Kuroda³

2004

Journal of Endocrinology

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Vascular endothelial growth factor (VEGF) is known to be necessary for the vascularization of the developing corpus luteum. Our recent data suggested that cyclooxygenase-II (COX-II) may play a role in the formation of vascular plexuses in developing corpora lutea of the rat. Here we examined the relationship between VEGF and the expression of prostaglandin (PG)-metabolizing enzymes in rat ovarian luteal cells. VEGF treatment caused a dosedependent increase in the expression of COX-II and membrane-associated PGE synthase (mPGES) mRNA in cultured rat luteal cells. However, pretreatment of the luteal cells with a selective COX-II inhibitor, NS-398, abolished the VEGF-enhanced mPGES mRNA expression. VEGF also increased PGE 2 secretion. Conversely, PGE 2 dose-dependently stimulated VEGF mRNA expression. Furthermore, VEGF induced VEGF mRNA expression, but this effect was abolished by NS-398 pretreatment. These findings suggest that VEGF enhances PGE 2 production by stimulating COX-II and mPGES expression in rat corpus luteum and that the effect of VEGF on luteal cells may be partially mediated by this stimulation of PGE 2 production.

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Section: Discussionsupporting

confidence: 87%

“…Several mechanisms are involved in regulating VEGF gene expression in the ovary (Ravindranath et al 1992, Neulen et al 1995, Christenson & Stouffer 1997, Pai et al 2001. PGE 2 -elicited cAMP is known to be one of the mediators of VEGF expression (Lopez Bernal et al 1995).…”

Section: Discussionmentioning

confidence: 99%

Vascular endothelial growth factor increases messenger RNAs encoding cyclooxygenase-II and membrane-associated prostaglandin E synthase in rat luteal cells

Sakurai¹,

Tamura²,

Kuroda³

2004

Journal of Endocrinology

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“…24,25 After liver resection, this cytokine is first expressed in periportal hepatocytes starting at 24 hours after PH and is involved in proliferation of parenchymal cells. 16 Because in other tissues PGs influence the production of VEGF, 12,13,26 we analyzed the expression of VEGF in the livers of rats treated with NS-398. Different molecular species of rat VEGF (120, 164, and 188 amino acids, named VEGF 120 , VEGF 164 , and VEGF 188 , respectively) are translated from different transcripts produced by al-ternative splicing.…”

Section: Effects Of Cox-2 Inhibitor On Liver Regenerationmentioning

confidence: 99%

Interplay among cardiotrophin-1, prostaglandins, and vascular endothelial growth factor in rat liver regeneration

et al. 2005

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Prostaglandins are hepatoprotective molecules generated in liver regeneration by the rapid induction of cyclooxygenase-2 (COX-2). Cardiotrophin-1 (CT-1) and vascular endothelial growth factor (VEGF) are other hepatoprotective mediators upregulated at 24 hours after partial hepatectomy. The interactions among these molecules during liver regeneration have not yet been defined. Here we show that rats subjected to partial hepatectomy treated with NS-398, a specific COX-2 inhibitor, exhibited cell cycle arrest, increased hepatocyte apoptosis, persistent extracellular signal-regulated kinase (ERK) 1/2 activation, and increased interleukin-6 production. These changes were associated with downregulation of CT-1 and COX-1 and altered pattern of VEGF expression. Administration of an adenovirus encoding CT-1 to NS-398-treated rats restituted normal levels of COX-1, prostaglandins, and VEGF in the liver after partial hepatectomy and restored normal liver regeneration. Furthermore, the stimulation of isolated rat hepatocytes with CT-1 increased COX-1, COX-2, and VEGF messenger RNAs and prostaglandin synthesis. Conversely, the addition of prostaglandin E1 to the culture increased CT-1 and VEGF production. In conclusion, COX-2 activation and production of prostaglandins soon after partial hepatectomy are essential requirements for hepatocyte proliferation and for the correct induction of both CT-1 and VEGF. CT-1 can restore liver regeneration after COX-2 inhibition by increasing VEGF, COX-1 expression, and prostaglandin synthesis. (HEPATOLOGY 2005;41:460-469.)

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“…Prostaglandins stimulate angiogenesis but the precise mechanisms of their proangiogenic actions remain unexplained. In various cancer tissues prostaglandin E 2 (PGE 2 ) stimulates VEGF expression (4). On the other hand, the cyclooxygenase-2 (COX-2) inhibitor, NS-398, restores tumour cell apoptosis, reduces microvascular density and reduces tumour growth of PC-3 prostate carcinoma cells xenografted into nude mice (5).…”

Section: Introductionmentioning

confidence: 99%

Circulating vascular endothelial growth factor and active renin concentrations and prostaglandin E2 urinary excretion in patients with adrenal tumours

Zacharieva

Atanassova

Orbetzova

et al. 2004

European Journal of Endocrinology

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PGE2 Stimulates VEGF Expression in Endothelial Cells via ERK2/JNK1 Signaling Pathways

Cited by 179 publications

References 31 publications

Vascular endothelial growth factor increases messenger RNAs encoding cyclooxygenase-II and membrane-associated prostaglandin E synthase in rat luteal cells

Vascular endothelial growth factor increases messenger RNAs encoding cyclooxygenase-II and membrane-associated prostaglandin E synthase in rat luteal cells

Interplay among cardiotrophin-1, prostaglandins, and vascular endothelial growth factor in rat liver regeneration

Circulating vascular endothelial growth factor and active renin concentrations and prostaglandin E2 urinary excretion in patients with adrenal tumours

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