Resveratrol inhibits high glucose-induced activation of AP-1 and NF-κB via SphK1/S1P2 pathway to attenuate mesangial cells proliferation and inflammation

Deng, Yanhui; Gong, Wenyan; Li, Qiang; Wu, Xian; Wu, Liyao; Zheng, Xueli; Chen, Wenying; Huang, Heqing

doi:10.1016/j.jff.2019.02.014

Cited by 6 publications

(8 citation statements)

References 47 publications

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“…RSV could reduce renal hypertrophy and ECM accumulation in diabetic model animals, 13,[31][32][33] and suppresses mesangial cells' proliferation under high glucose conditions. 13,22,34 Here, we showed that RSV obviously reversed LPS-stimulated mesangial cell proliferation. RSV at the concentration over 40 µM exhibited cytotoxicity in RMCs (data not shown).…”

Section: Discussionmentioning

confidence: 66%

“…These results were similar with our previous study which was performed in high glucose conditions. 22 S1P2, as one of the S1P receptors, is primarily expressed in mesangial cells and play an important role in DN. 38 S1P2 receptor mediated S1P-induced mesangial cell proliferation and FN upregulation through activating high glucose-induced MAPK pathway.…”

Section: Discussionmentioning

confidence: 99%

“…12,24 Our research group illuminated that RSV could effectively ameliorate the renal function of STZ-induced diabetic rats, 31 and attenuate cell proliferation and inflammation via inhibiting high glucose-induced SphK1/S1P2 pathway. 22 To investigate whether the potential mechanism of RSV was independent of its hypoglycemic effect, we observed the effect of RSV on the activation of SphK1/ S1P2 pathway in RMCs under LPS stimulation. Firstly, SphK1 and S1P2 expression were examined at different times under LPS stimulation.…”

Section: Effects Of Rsv On Sphk1/s1p2 Pathway In Lps-induced Rmcs' Prmentioning

confidence: 99%

“…[18][19][20][21]29 Recently, we found that RSV prevented high glucoseinduced rat glomerular mesangial cells' (RMCs) proliferation, inflammatory factors' expression and the activation of AP-1 and NF-κB through SphK1/S1P2 pathway. 22 Nevertheless, it has not been clarified whether the inhibitory effect of RSV on SphK1/S1P2 is indirectly associated with its hypoglycemic effect or not. In addition, it has not been addressed whether the protective effect of RSV on DN is due to SphK1/S1P2-dependent depression of NF-κB.…”

Section: Introductionmentioning

confidence: 99%

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<p>Resveratrol Inhibits Lipopolysaccharide-Induced Extracellular Matrix Accumulation and Inflammation in Rat Glomerular Mesangial Cells by SphK1/S1P2/NF-κB Pathway</p>

Gong¹,

Li²,

Chen³

et al. 2020

DMSO

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Chronic inflammation plays a key role in the pathogenesis of various diseases such as diabetic nephropathy (DN). Resveratrol (RSV), a natural polyphenol, has been proven to have renoprotective effects. In this study, we used a lipopolysaccharide (LPS)induced rat glomerular mesangial cells (RMCs) model, to elucidate the renoprotective effect of RSV on sphingosine kinase 1 (SphK1)/sphingosine 1-phosphate receptor 2 (S1P2)/NF-κB activation and the expression of downstream inflammatory mediators, such as intercellular adhesion molecule-1 (ICAM-1), inducible nitric oxide synthase (iNOS) and fibronectin (FN) protein expression in RMCs. Methods: Cell proliferation was tested by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT). The protein levels of FN, ICAM-1, iNOS, SphK1, S1P2 and NF-κB p65 in RMCs were detected by Western blot. The DNA-binding activity of NF-κB was detected by electrophoretic mobility shift assay (EMSA). SphK1 activity and S1P content were measured by using sphingosine kinase activity assay kit and ELISA assay, respectively. Results: We first found that LPS could stimulate SphK1/S1P axis activation, whereas this occurrence was significantly blocked by RSV pretreatment. RSV obviously repressed LPSinduced upregulated expression of fibronectin (FN), intercellular adhesion molecule-1 (ICAM-1) and inducible nitric oxide synthase (iNOS) in RMCs. Moreover, RSV markedly reduced SphK1 activity and its protein expression, and attenuated S1P content in LPSinduced RMCs. Furthermore, RSV could block LPS-induced upregulation of NF-κB p65 and DNA-binding activity of NF-κB. And this phenomenon was notably attenuated by SphK1 inhibitor and S1P2 inhibitor. Conclusion: RSV inhibited LPS-induced RMCs' proliferation and inflammation and FN expression by SphK1/S1P2/NF-κB pathway, suggesting that RSV may be independent of its hypoglycemic effect on preventing or delaying the development of mesangial cell fibrosis.

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Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Section: Effects Of Rsv On Sphk1/s1p2 Pathway In Lps-induced Rmcs' Prmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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<p>Resveratrol Inhibits Lipopolysaccharide-Induced Extracellular Matrix Accumulation and Inflammation in Rat Glomerular Mesangial Cells by SphK1/S1P2/NF-κB Pathway</p>

Gong¹,

Li²,

Chen³

et al. 2020

DMSO

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“…NF-κB signaling is an inducer of LPS, as well as MAPK signaling, while the attenuation of this signaling by resveratrol contributes to its anti-inflammatory effect [10,38]. NF-κB and AP-1 were key downstream factors of TLR4 and resveratrol was shown to block the expression of TLR4 and suppress the phosphorylation of NF-κB and expression of AP-1 in high glucose-induced mesangial cells [39]. In this study, resveratrol prevented NF-κB and TLR4 gene upregulation caused by LPS.…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Resveratrol Improves Systemic Inflammation Responses in LPS-Injected Lambs

Liang

Zhou

et al. 2019

Animals

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Simple SummaryChina’s livestock industry has been transforming from traditional extensive systems to highly intensive systems. Highly intensive livestock production often causes immune stress to animals, which makes them more susceptible to infections. The aim of this study was to examine whether resveratrol alleviates inflammation in lambs. Results showed that resveratrol attenuated the LPS-evoked inflammatory responses in lambs by suppressing expression levels of inflammatory cytokines and blocking NF-κB and MAPK signaling pathways. Based on these studies, resveratrol has the potential to be a promising therapeutic reagent for multiple inflammatory illnesses caused by immune stress. AbstractHighly intensive livestock production often causes immune stress to animals, which makes them more susceptible to infections. The aim of this study was to examine whether resveratrol (Res) alleviates inflammation in lambs. In Experiment 1, 16 male lambs were injected with lipopolysaccharides (LPS) at an initial dose of 0.25, 1.25, and 2.5 μg/kg body weight (BW) for 9 days. Average daily gain and blood parameters were measured and clinical symptoms were recorded. In Experiment 2, 20 male lambs were injected intravenously with LPS (0 mg/kg) + Res (0 mg), LPS (2.5 μg /kg) + Res (0 mg, 82.5 mg, 165 mg, 330 mg), 4 h after LPS injection. Jugular blood was collected from each lamb to determine white blood cell (WBC) counts and the expression of inflammatory genes. In Experiment 1, all LPS-treated lambs showed clinical signs of sickness including rhinorrhea, lethargy, and shivering, and systemic inflammatory responses of increased inflammatory genes levels and cortisol concentration. The lambs had increased respiratory and heart rates and rectal temperature and decreased average daily gain and feed intake. In Experiment 2, resveratrol significantly reduced WBCs and the expression levels of several genes associated with inflammation response (TLR4, NF-κB, c-jun) and inhibited the signaling cascades of NF-κB and MAPKs by down-regulating the expression levels of inflammatory cytokines (IL-1β, IL-4, IL-6, TNF-α, IFN-γ) induced by LPS. Resveratrol attenuated the LPS-evoked inflammatory responses in lambs by suppressing expression levels of inflammatory cytokines, and blocking NF-κB and MAPK signaling pathways.

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Inhibitory Effect of Resveratrol on LPS-induced Glomerular Mesangial Cells Proliferation and TGF-β1 Expression via Sphingosine Kinase 1 Pathway

Feng

Gong

et al. 2022

Chin. J. Integr. Med.

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Resveratrol inhibits high glucose-induced activation of AP-1 and NF-κB via SphK1/S1P2 pathway to attenuate mesangial cells proliferation and inflammation

Cited by 6 publications

References 47 publications

<p>Resveratrol Inhibits Lipopolysaccharide-Induced Extracellular Matrix Accumulation and Inflammation in Rat Glomerular Mesangial Cells by SphK1/S1P2/NF-κB Pathway</p>

<p>Resveratrol Inhibits Lipopolysaccharide-Induced Extracellular Matrix Accumulation and Inflammation in Rat Glomerular Mesangial Cells by SphK1/S1P2/NF-κB Pathway</p>

Protective Effect of Resveratrol Improves Systemic Inflammation Responses in LPS-Injected Lambs

Inhibitory Effect of Resveratrol on LPS-induced Glomerular Mesangial Cells Proliferation and TGF-β1 Expression via Sphingosine Kinase 1 Pathway

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