Resveratrol Inhibits Lipopolysaccharide-Induced Extracellular Matrix Accumulation and Inflammation in Rat Glomerular Mesangial Cells by SphK1/S1P2/NF-κB Pathway
Wenyan Gong,1,* Jie Li,2,* Wenying Chen,3 Fuzhen Feng,3 Yanhui Deng3 1Department of Cardiology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou 310000, People’s Republic of China; 2Medical Research Center, Guangdong Second Provincial General Hosp...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2020-11-01
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| Series: | Diabetes, Metabolic Syndrome and Obesity |
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| Online Access: | https://www.dovepress.com/resveratrol-inhibits-lipopolysaccharide-induced-extracellular-matrix-a-peer-reviewed-article-DMSO |
| _version_ | 1797935040974290944 |
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| author | Gong W Li J Chen W Feng F Deng Y |
| author_facet | Gong W Li J Chen W Feng F Deng Y |
| author_sort | Gong W |
| collection | DOAJ |
| description | Wenyan Gong,1,* Jie Li,2,* Wenying Chen,3 Fuzhen Feng,3 Yanhui Deng3 1Department of Cardiology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou 310000, People’s Republic of China; 2Medical Research Center, Guangdong Second Provincial General Hospital, Guangzhou 510317, People’s Republic of China; 3Department of Pharmacy, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yanhui DengDepartment of Pharmacy, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, People’s Republic of ChinaTel +86 20 62784810Email shiningdyh@sina.comPurpose: 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 LPS-induced 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 LPS-induced 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.Keywords: diabetic nephropathy, resveratrol, lipopolysaccharide, sphingosine kinase 1, sphingosine 1-phosphate, NF-κB |
| first_indexed | 2024-04-10T18:08:17Z |
| format | Article |
| id | doaj.art-82c81c17f93049c0ab96cd4794da5027 |
| institution | Directory Open Access Journal |
| issn | 1178-7007 |
| language | English |
| last_indexed | 2024-04-10T18:08:17Z |
| publishDate | 2020-11-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Diabetes, Metabolic Syndrome and Obesity |
| spelling | doaj.art-82c81c17f93049c0ab96cd4794da50272023-02-02T11:50:39ZengDove Medical PressDiabetes, Metabolic Syndrome and Obesity1178-70072020-11-01Volume 134495450559536Resveratrol Inhibits Lipopolysaccharide-Induced Extracellular Matrix Accumulation and Inflammation in Rat Glomerular Mesangial Cells by SphK1/S1P2/NF-κB PathwayGong WLi JChen WFeng FDeng YWenyan Gong,1,* Jie Li,2,* Wenying Chen,3 Fuzhen Feng,3 Yanhui Deng3 1Department of Cardiology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou 310000, People’s Republic of China; 2Medical Research Center, Guangdong Second Provincial General Hospital, Guangzhou 510317, People’s Republic of China; 3Department of Pharmacy, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yanhui DengDepartment of Pharmacy, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, People’s Republic of ChinaTel +86 20 62784810Email shiningdyh@sina.comPurpose: 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 LPS-induced 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 LPS-induced 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.Keywords: diabetic nephropathy, resveratrol, lipopolysaccharide, sphingosine kinase 1, sphingosine 1-phosphate, NF-κBhttps://www.dovepress.com/resveratrol-inhibits-lipopolysaccharide-induced-extracellular-matrix-a-peer-reviewed-article-DMSOdiabetic nephropathyresveratrollipopolysaccharidesphingosine kinase 1sphingosine 1-phosphatenf-κb |
| spellingShingle | Gong W Li J Chen W Feng F Deng Y Resveratrol Inhibits Lipopolysaccharide-Induced Extracellular Matrix Accumulation and Inflammation in Rat Glomerular Mesangial Cells by SphK1/S1P2/NF-κB Pathway Diabetes, Metabolic Syndrome and Obesity diabetic nephropathy resveratrol lipopolysaccharide sphingosine kinase 1 sphingosine 1-phosphate nf-κb |
| title | Resveratrol Inhibits Lipopolysaccharide-Induced Extracellular Matrix Accumulation and Inflammation in Rat Glomerular Mesangial Cells by SphK1/S1P2/NF-κB Pathway |
| title_full | Resveratrol Inhibits Lipopolysaccharide-Induced Extracellular Matrix Accumulation and Inflammation in Rat Glomerular Mesangial Cells by SphK1/S1P2/NF-κB Pathway |
| title_fullStr | Resveratrol Inhibits Lipopolysaccharide-Induced Extracellular Matrix Accumulation and Inflammation in Rat Glomerular Mesangial Cells by SphK1/S1P2/NF-κB Pathway |
| title_full_unstemmed | Resveratrol Inhibits Lipopolysaccharide-Induced Extracellular Matrix Accumulation and Inflammation in Rat Glomerular Mesangial Cells by SphK1/S1P2/NF-κB Pathway |
| title_short | Resveratrol Inhibits Lipopolysaccharide-Induced Extracellular Matrix Accumulation and Inflammation in Rat Glomerular Mesangial Cells by SphK1/S1P2/NF-κB Pathway |
| title_sort | resveratrol inhibits lipopolysaccharide induced extracellular matrix accumulation and inflammation in rat glomerular mesangial cells by sphk1 s1p2 nf kappa b pathway |
| topic | diabetic nephropathy resveratrol lipopolysaccharide sphingosine kinase 1 sphingosine 1-phosphate nf-κb |
| url | https://www.dovepress.com/resveratrol-inhibits-lipopolysaccharide-induced-extracellular-matrix-a-peer-reviewed-article-DMSO |
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