Signalling mechanisms in sphingosine 1‐phosphate‐promoted mesangial cell proliferation

Katsuma, Susumu; Hada, Yuko; Ueda, Toshihiro; Shiojima, Satoshi; Hirasawa, Akira; Tanoue, Akito; Takagaki, Kazuchika; Ohgi, Tadaaki; Yano, Junichi; Tsujimoto, Gozoh

doi:10.1046/j.1365-2443.2002.00594.x

Cited by 66 publications

(79 citation statements)

References 33 publications

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“…In the present study we provide evidence for a novel type of transactivation between GPCRs exemplified by the S1P receptors and the TGF-␤ receptor family. Mesangial cells do express S1P [1][2][3][4][5] (28), and it has recently been suggested that especially S1P 2 and S1P 3 are involved in the mitogenic function of S1P in these cells (28). The authors also propose a crossactivation of the PDGF receptor cascade.…”

Section: Discussionmentioning

confidence: 99%

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Sphingosine 1-Phosphate Cross-activates the Smad Signaling Cascade and Mimics Transforming Growth Factor-β-induced Cell Responses

Xin

Ren

Kleuser

et al. 2004

Journal of Biological Chemistry

172

143

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Exposure of renal mesangial cells to sphingosine 1-phosphate (S1P) leads to a rapid and transient activation of the mitogen-and stress-activated protein kinases but also the protein kinase B. Here, we show that S1P also induces phosphorylation of Smad proteins, which are members of the transforming growth factor-␤ (TGF-␤) signaling device. However, Smad phosphorylation occurred more slowly with a maximal effect after 20 -30 min of S1P stimulation when compared with the rapid activation of the MAPKs. Interestingly, Smad phosphorylation is increased by pertussis toxin, which is in contrast to the complete inhibition of S1P-induced MAPK phosphorylation by pertussis toxin. TGF-␤ is a potent anti-inflammatory cytokine, which in mesangial cells attenuates the expression of (i) inducible nitricoxide synthase (iNOS) caused by interleukin (IL)-1␤, (ii) secreted phospholipase A 2 (sPLA 2 ), and (iii) matrix metalloproteinase-9 (MMP-9). These gene products are also down-regulated by S1P in a concentration-dependent manner. Furthermore, the expression of connective tissue growth factor is enhanced by both TGF-␤ 2 and S1P. These effects of S1P are not mediated by the MAPK cascade as neither pertussis toxin nor the MAPK cascade inhibitor U0126 are able to reverse this inhibition. Overexpression of the inhibitory Smad-7 or down-regulation of co-Smad-4 lead to a reversal of the blocking effect of S1P on IL-1␤-induced NO release. Moreover, down-regulating the TGF-␤ receptor type II by the siRNA technique or antagonizing the S1P 3 receptor subtype with suramin abrogates S1P-stimulated Smad phosphorylation. In summary, our data show that S1P trans-activates the TGF-␤ receptor and triggers activation of Smads followed by activation of connective tissue growth factor gene transcription and inhibition of IL-1␤-induced expression of iNOS, sPLA 2 , and MMP-9.

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Section: Discussionmentioning

confidence: 99%

“…In renal mesangial cells, several S1P receptors are expressed, including the S1P 1 , S1P 2 , S1P 3 , S1P 4 , and S1P 5 (formerly known as Edg-1, -5, -3, -6, and -8 receptors) (28), which mediate many effects of S1P including mobilization of intracellular calcium, activation of the classical MAPK cascade, and cell proliferation (28).…”

mentioning

confidence: 99%

Sphingosine 1-Phosphate Cross-activates the Smad Signaling Cascade and Mimics Transforming Growth Factor-β-induced Cell Responses

Xin

Ren

Kleuser

et al. 2004

Journal of Biological Chemistry

172

143

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“…Caspase-3 Activity Assay-The activity of caspase-3 was determined by the EnzChek Caspase-3 Assay Kit (Molecular Probes) following the manufacturer's instructions (12). Briefly, 3 ϫ 10 6 cells were serumstarved for 2 h and treated with the indicated reagents.…”

Section: Methodsmentioning

confidence: 99%

“…DNA Fragmentation Assay-DNA fragmentation was measured using the Cell Death Detection ELISA PLUS kit (Roche Applied Science) following the manufacturer's instructions (12). Briefly, STC-1 cells, cultured in 24-well culture plates, were treated with the indicated reagents.…”

Section: Methodsmentioning

confidence: 99%

Free Fatty Acids Inhibit Serum Deprivation-induced Apoptosis through GPR120 in a Murine Enteroendocrine Cell Line STC-1

Katsuma

Hatae

Yano

et al. 2005

Journal of Biological Chemistry

Self Cite

168

101

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“…A balance between Cer and other bioactive metabolites such as sphingosine (Sph) and sphingosine-1-phosphate (S1P) has been pointed out as a sensitive rheostat controlling growth and death of various cell types (14,15). Thus, in contrast to the growth-inhibitory and proapoptotic effects of Cer and Sph (16 -20), S1P has been shown to promote cell growth in various cell types including MC (21,22). Many studies have reported the involvement of sphingomyelinases, the ceramide-generating enzymes, in the regulation of Cer levels in response to proinflammatory cytokines, growth factors, or stress stimuli (23,24).…”

mentioning

confidence: 99%

Bimodal Effect of Advanced Glycation End Products on Mesangial Cell Proliferation Is Mediated by Neutral Ceramidase Regulation and Endogenous Sphingolipids

Geoffroy

Wiernsperger

Lagarde

et al. 2004

Journal of Biological Chemistry

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Advanced glycation end-products (AGE) are generated by chronic hyperglycaemia and may cause diabetic microvascular complications such as diabetic nephropathy. Many factors influence the development of diabetic nephropathy; however, dysregulation of mesangial cell (MC) proliferation appears to play an early and crucial role. In this study, we investigated the effects of AGE on rat MC proliferation and the involvement of sphingolipids in the AGE response. Results show a bimodal effect of AGE on MC proliferation. Thus, low AGE concentrations (<1 M) induced a significant increase (؉26%) of MC proliferation, whereas higher concentrations (10 M) markedly reduced it (؊24%). In parallel, AGE exerted biphasic effects on neutral ceramidase expression and activity. Low AGE concentrations increased neutral ceramidase activity and expression, whereas high AGE concentrations showed opposite effects. Surprisingly, neutral ceramidase modulation did not result in changes of ceramide levels. However, the AGE (10 M)-inhibitory effect on MC proliferation was associated with accumulation of sphingosine and was specifically prevented by blocking glucosylceramide synthesis, suggesting that the high AGE concentration effects are mediated by sphingosine and/or glycolipids. On the other hand, treatment of cells with low AGE concentrations led to an increase of sphingosine kinase activity and sphingosine-1-phosphate production that drove the increase of MC proliferation. Interestingly, in glomeruli isolated from streptozotocin-diabetic rats, a time-dependent modulation of ceramidase activity was observed as compared with controls. These results suggest that AGE regulate MC growth by modulating neutral ceramidase and endogenous sphingolipids.

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Signalling mechanisms in sphingosine 1‐phosphate‐promoted mesangial cell proliferation

Cited by 66 publications

References 33 publications

Sphingosine 1-Phosphate Cross-activates the Smad Signaling Cascade and Mimics Transforming Growth Factor-β-induced Cell Responses

Sphingosine 1-Phosphate Cross-activates the Smad Signaling Cascade and Mimics Transforming Growth Factor-β-induced Cell Responses

Free Fatty Acids Inhibit Serum Deprivation-induced Apoptosis through GPR120 in a Murine Enteroendocrine Cell Line STC-1

Bimodal Effect of Advanced Glycation End Products on Mesangial Cell Proliferation Is Mediated by Neutral Ceramidase Regulation and Endogenous Sphingolipids

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