Expression of mouse membrane-associated prostaglandin E2 synthase-2 (mPGES-2) along the urogenital tract

Yang, Guangrui; Chen, Lihong; Zhang, Yahua; Zhang, Xiaoyan; Wu, Jing; Li, Shuo; Wei, Miaoyan; Zhang, Zhiwen; Breyer, Matthew D.; Guan, You-Fei

doi:10.1016/j.bbalip.2006.06.018

Cited by 29 publications

(25 citation statements)

References 56 publications

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“…64 Low levels of mPGES2 and cPGES are also detected in the kidney. 66,67 Thromboxane synthase is mainly detected in glomeruli. 65 to be mainly localized to vasculature in the kidney.…”

Section: Cox-derived Prostanoidsmentioning

confidence: 99%

Physiologic and pathophysiologic roles of lipid mediators in the kidney

Hao

Breyer

2007

Kidney International

148

120

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Small lipids such as eicosanoids exert diverse and complex functions. In addition to their role in regulating normal kidney function, these lipids also play important roles in the pathogenesis of kidney diseases. Cyclooxygenase (COX)-derived prostanoids play important role in maintaining renal function, body fluid homeostasis, and blood pressure. Renal cortical COX2-derived prostanoids, particularly (PGI2) and PGE2 play critical roles in maintaining blood pressure and renal function in volume contracted states. Renal medullary COX2-derived prostanoids appear to have antihypertensive effect in individuals challenged with a high salt diet. 5-Lipoxygenase (LO)-derived leukotrienes are involved in inflammatory glomerular injury. LO product 12-hydroxyeicosatetraenoic acid (12-HETE) is associated with pathogenesis of hypertension, and may mediate angiotensin II and TGFbeta induced mesengial cell abnormality in diabetic nephropathy. P450 hydroxylase-derived 20-HETE is a potent vasoconstrictor and is involved in the pathogenesis of hypertension. P450 epoxygenase derived epoxyeicosatrienoic acids (EETs) have vasodilator and natriuretic effect. Blockade of EET formation is associated with salt-sensitive hypertension. Ceramide has also been demonstrated to be an important signaling molecule, which is involved in pathogenesis of acute kidney injury caused by ischemia/reperfusion, and toxic insults. Those pathways should provide fruitful targets for intervention in the pharmacologic treatment of renal disease.

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“…64 Low levels of mPGES2 and cPGES are also detected in the kidney. 66,67 Thromboxane synthase is mainly detected in glomeruli. 65 to be mainly localized to vasculature in the kidney.…”

Section: Cox-derived Prostanoidsmentioning

confidence: 99%

Physiologic and pathophysiologic roles of lipid mediators in the kidney

Hao

Breyer

2007

Kidney International

148

120

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“…whereas the expression of mPGES-2 and cPGES is rather constitutive. Within the kidney, cPGES was mainly expressed in the collecting duct (39) while mPGES-2 had a wide distribution (38). Recently, mice have been engineered with specific deletions in each of these three PGES enzymes.…”

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confidence: 99%

mPGES-1 deletion potentiates urine concentrating capability after water deprivation

Liu

Downton

Dong

et al. 2012

American Journal of Physiology-Renal Physiology

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PGE(2) plays an important role in the regulation of fluid metabolism chiefly via antagonizing vasopressin-induced osmotic permeability in the distal nephron, but its enzymatic sources remain uncertain. The present study was undertaken to investigate the potential role of microsomal PGE synthase (mPGES)-1 in the regulation of urine concentrating ability after water deprivation (WD). Following 24-h WD, wild-type (WT) mice exhibited a significant reduction in urine volume, accompanied by a significant elevation in urine osmolality compared with control groups. In contrast, in response to WD, mPGES-1 knockout (KO) mice had much less urine volume and higher urine osmolality. Analysis of plasma volume by measurement of hematocrit and by using a nanoparticle-based method consistently demonstrated that dehydrated WT mice were volume depleted, which was significantly improved in the KO mice. WD induced a twofold increase in urinary PGE(2) output in WT mice, which was completely blocked by mPGES-1 deletion. At baseline, the KO mice had a 20% increase in V(2) receptor mRNA expression in the renal medulla but not the cortex compared with WT controls; the expression was unaffected by WD irrespective of the genotype. In response to WD, renal medullary aquaporin-2 (AQP2) mRNA exhibited a 60% increase in WT mice, and this increase was greater in the KO mice. Immunoblotting demonstrated increased renal medullary AQP2 protein abundance in both genotypes following WD, with a greater increase in the KO mice. Similar results were obtained by using immunohistochemistry. Paradoxically, plasma AVP response to WD seen in WT mice was absent in the KO mice. Taken together, these results suggest that mPGES-1-derived PGE(2) reduces urine concentrating ability through suppression of renal medullary expression of V(2) receptors and AQP2 but may enhance it by mediating the central AVP response.

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“…Immunohistochemistry was performed as previously described [35] . Briefly, segments of thoracic aortas, mesenteric arteries and kidneys were isolated from wild-type and mPGES-1 -/-mice and fixed in 4% paraformaldehyde overnight at 4 °C.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Enhanced pressor response to acute Ang II infusion in mice lacking membrane-associated prostaglandin E2 synthase-1

Zhang

Yang

et al. 2010

Acta Pharmacol Sin

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Aim: To examine the contribution of vascular membrane-associated prostaglandin E2 synthase-1 (mPGES-1) to acute blood pressure homeostasis. Methods: Angiotensin II (AngII, 75 pmol·kg -1 ·min -1 ) was continuously infused via the jugular vein into wild-type and mPGES-1 -/-mice for 30 min, and blood pressure was measured by carotid arterial catheterization. RT-PCR and immunohistochemistry were performed to detect the expression and localization of mPGES-1 in the mouse arterial vessels. Mesenteric arteries were dissected from mice of both genotypes to study vessel tension and measure vascular PGE2 levels. Results: Wild-type and mPGES-1 -/-mice showed similar blood pressure levels at baseline, and the acute intravenous infusion of AngII caused a greater increase in mean arterial pressure in the mPGES-1 -/-group, with a similar diuretic and natriuretic response in both groups. mPGES-1 was constitutively expressed in the aortic and mesenteric arteries and vascular smooth muscle cells of wild-type mice. Strong staining was detected in the smooth muscle layer of arterial vessels. Ex vivo treatment of mesenteric arteries with AngII produced more vasodilatory PGE2 in wild-type than in mPGES-1 -/-mice. In vitro tension assays further revealed that the mesenteric arteries of mPGES-1 -/-mice exhibited a greater vasopressor response to AngII than those arteries of wild-type mice. Conclusion: Vascular mPGES-1 acts as an important tonic vasodilator, contributing to acute blood pressure regulation.Keywords: prostaglandin E2; membrane-associated prostaglandin E2 synthase-1; angiotensin II; blood pressure; resistant vessel Acta Pharmacologica Sinica (2010Sinica ( ) 31: 1284Sinica ( -1292 doi: 10.1038/aps.2010 published online 27 Sep 2010 Original Article * To whom correspondence should be addressed. [14] , but its relative contribution to PGE2 generation in vivo remains largely uncharacterized. The third form of PGES (cPGES) was originally isolated from cytoplasmic extracts and is expressed ubiquitously in a constitutive housekeeping manner and functionally coupled with COX-1 to generate physiological PGE2 [15,16] . A large body of evidence demonstrates that PGE2 exerts both vasoconstrictive and vasodilatory actions via its four G-protein coupled receptors: EP1, EP2, EP3, and EP4 [17,18] . However, the net effect of PGE2 appears to be the reduction of blood pressure [19][20][21] . This finding is consistent with clinical observations that nonsteroidal anti-inflammatory drugs (NSAIDs), such as COX inhibitors, can cause hypertension [22][23][24] . Similarly, COX-2 inhibitors increase blood pressure in both animals and patients [25][26][27][28] , which suggests that COX-2-derived prostaglandins are predominantly the vasodilators. Since mPGES-1 is generally believed to be coupled with COX-2 to mediate PGE2 biosynthesis, mPGES-1-derived PGE2 may also exert a vasodepressor effect in vivo. Indeed, recent studies found that deletion of the mPGES-1 gene caused a hypersensitive phenotype in response to chronic salt loading and angiotens...

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Expression of mouse membrane-associated prostaglandin E2 synthase-2 (mPGES-2) along the urogenital tract

Cited by 29 publications

References 56 publications

Physiologic and pathophysiologic roles of lipid mediators in the kidney

Physiologic and pathophysiologic roles of lipid mediators in the kidney

mPGES-1 deletion potentiates urine concentrating capability after water deprivation

Enhanced pressor response to acute Ang II infusion in mice lacking membrane-associated prostaglandin E2 synthase-1

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