Unbalanced expression of sphingosine 1-phosphate receptors in diabetic nephropathy

Imasawa, Toshiyuki; Kitamura, Hiroshi; Ohkawa, Ryunosuke; Satoh, Yumiko; Miyashita, Akiko; Yatomi, Yutaka

doi:10.1016/j.etp.2009.02.068

Cited by 30 publications

(25 citation statements)

References 29 publications

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“…detected in whole kidney tissue, renal medulla, and glomeruli 11,12 ; however, the distribution of S1P receptor expression in the renal microvasculature has not been studied. We demonstrate here that both S1P1 and S1P2 proteins are abundantly present in isolated preglomerular microvessels, whereas S1P3, S1P4, and S1P5 receptor protein expression was not detected.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the lack of detection of S1P4 receptors in renal microvessels agrees with the findings of Ota et al, who reported positive staining for S1P4 receptor protein in pulmonary arteries but not intrarenal arteries. 39 Furthermore, to distinguish between endothelial or tubular cell expression, 11,12 we isolated MVSMCs from preglomerular microvessels. Consistent with Western blot data, S1P1 and S1P2, but not S1P3, receptors were strongly detected in isolated MVSMCs.…”

Section: Discussionmentioning

confidence: 99%

“…[3][4][5] Studies in animals show that application of exogenous S1P causes either vasoconstriction or vasodilation of isolated arteries from several vascular beds. 3,4 Although S1P receptor expression is detected in kidneys, [11][12][13] little is known about the effects of S1P on renal microvascular function. Early studies showed that S1P evoked vasoconstriction in isolated intrarenal arteries.…”

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confidence: 99%

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Sphingosine-1-Phosphate Evokes Unique Segment-Specific Vasoconstriction of the Renal Microvasculature

Guan¹,

Singletary²,

Cook³

et al. 2014

Journal of the American Society of Nephrology

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Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, has been implicated in regulating vascular tone and participating in chronic and acute kidney injury. However, little is known about the role of S1P in the renal microcirculation. Here, we directly assessed the vasoresponsiveness of preglomerular and postglomerular microvascular segments to exogenous S1P using the in vitro blood-perfused juxtamedullary nephron preparation. Superfusion of S1P (0.001-10 mM) evoked concentration-dependent vasoconstriction in preglomerular microvessels, predominantly afferent arterioles. After administration of 10 mM S1P, the diameter of afferent arterioles decreased to 35%65% of the control diameter, whereas the diameters of interlobular and arcuate arteries declined to 50%612% and 68%66% of the control diameter, respectively. Notably, efferent arterioles did not respond to S1P. The S1P receptor agonists FTY720 and FTY720-phosphate and the specific S1P1 receptor agonist SEW2871 each evoked modest afferent arteriolar vasoconstriction. Conversely, S1P2 receptor inhibition with JTE-013 significantly attenuated S1P-mediated afferent arteriolar vasoconstriction. Moreover, blockade of L-type voltage-dependent calcium channels with diltiazem or nifedipine attenuated S1P-mediated vasoconstriction. Intravenous injection of S1P in anesthetized rats reduced renal blood flow dose dependently. Western blotting and immunofluorescence revealed S1P1 and S1P2 receptor expression in isolated preglomerular microvessels and microvascular smooth muscle cells. These data demonstrate that S1P evokes segmentally distinct preglomerular vasoconstriction via activation of S1P1 and/or S1P2 receptors, partially via L-type voltagedependent calcium channels. Accordingly, S1P may have a novel function in regulating afferent arteriolar resistance under physiologic conditions. 25: 177425: -178525: , 201425: . doi: 10.1681 Sphingosine 1-phosphate (S1P) is recognized as an important signaling molecule in diverse biologic processes. 1,2 Growing evidence indicates that S1P plays an important role in regulating vascular reactivity. 3-5 S1P is a bioactive sphingolipid metabolite and is released from erythrocytes, platelets, and endothelial cells. 6,7 The majority of S1P effects are mediated via five distinct receptors (S1P1-S1P5 receptors), which represent a family of small G proteincoupled receptors (GPCRs) 5 ; however, S1P can also exist in the cytoplasm as a second messenger involved in Ca 2+ mobilization or cell survival and proliferation. 8,9 S1P1-S1P3 receptors are expressed by a wide variety of tissues, whereas S1P4 and S1P5 receptors are mainly expressed in cells of the immune and nervous systems. 4,10 In the vasculature, endothelial cells mainly express S1P1 and S1P3 with variable expression of S1P2, whereas vascular smooth muscle cells express S1P2 and S1P3 with variable expression of S1P1. [3][4][5] Studies in animals show that application of exogenous S1P J Am Soc Nephrol

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Sphingosine-1-Phosphate Evokes Unique Segment-Specific Vasoconstriction of the Renal Microvasculature

Guan¹,

Singletary²,

Cook³

et al. 2014

Journal of the American Society of Nephrology

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“…They include S1PR 1 -5 , and activation of S1P 1 is critical for immune cell trafficking [62]. However, in the glomeruli of rats with diabetic nephropathy, it was recently observed that S1P signals are preferentially transmitted through S1P 2 , rather than S1P 1 [63]. It is possible that this biased delivery of S1P signals may mediate the pathogenesis of endothelial injuries in diabetic nephropathy [63].…”

Section: S1p/s1pr Systemmentioning

confidence: 99%

“…However, in the glomeruli of rats with diabetic nephropathy, it was recently observed that S1P signals are preferentially transmitted through S1P 2 , rather than S1P 1 [63]. It is possible that this biased delivery of S1P signals may mediate the pathogenesis of endothelial injuries in diabetic nephropathy [63]. S1P 2 was also recently shown to be expressed in enteric neurons and migrating cranial crest cells, while expression of S1P 1 is significant in the neuroepithelium [64].…”

Section: S1p/s1pr Systemmentioning

confidence: 99%

Role of Smad3 and S1P Signaling in Mandibular Condylar Cartilage Homeostasis

Izawa¹,

Hutami²,

Mori³

et al. 2017

J Bone Res

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Osteoarthritis (OA), the most common degenerative joint disease, results from an imbalance between chondrocyte-controlled anabolic and catabolic processes. OA is characterized by progressive degradation of components of the Extracellular Matrix (ECM) within the articular cartilage, correlated with secondary inflammation. Several studies had investigated the morphological and biochemical changes during OA progression. However, a comprehensive study of the OA pathogenesis still remains to be elucidated to find the best therapy for OA. In this review, recent advances in our understanding of the mechanisms of action of Sphingosine 1-phosphate (S1P) and Smad3 independently and in relation to Temporomandibular Joint Osteoarthritis (TMJ-OA) will be discussed. S1P receptors are expressed on the cell surface and are internalized upon binding of the bioactive lipid, S1P, as part of the migratory response. Meanwhile, Smad3 is an intracellular signaling molecule that mediates signaling from transforming growth factor-β (TGF-β) and activin receptors. Crosstalk between the TGF-β/Smad3 and S1P/S1P 3 signaling pathways regulates cell motility and apoptosis in chondrocyte cells. Thus, Smad3/S1P 3 signaling in chondrocytes may be responsible for the development of TMJ-OA, and the potential for these proteins to represent targets for the treatment of TMJ-OA warrants further study.

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Sphingosine-1-phosphate induces differentiation of cultured renal tubular epithelial cells under Rho kinase activation via the S1P2 receptor

et al. 2014

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Unbalanced expression of sphingosine 1-phosphate receptors in diabetic nephropathy

Cited by 30 publications

References 29 publications

Sphingosine-1-Phosphate Evokes Unique Segment-Specific Vasoconstriction of the Renal Microvasculature

Sphingosine-1-Phosphate Evokes Unique Segment-Specific Vasoconstriction of the Renal Microvasculature

Role of Smad3 and S1P Signaling in Mandibular Condylar Cartilage Homeostasis

Sphingosine-1-phosphate induces differentiation of cultured renal tubular epithelial cells under Rho kinase activation via the S1P2 receptor

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