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...
Guardado en:
| Autores principales: | , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Dove Medical Press
2020
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/82c81c17f93049c0ab96cd4794da5027 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:82c81c17f93049c0ab96cd4794da5027 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:82c81c17f93049c0ab96cd4794da50272021-12-02T13:38:24ZResveratrol Inhibits Lipopolysaccharide-Induced Extracellular Matrix Accumulation and Inflammation in Rat Glomerular Mesangial Cells by SphK1/S1P2/NF-κB Pathway1178-7007https://doaj.org/article/82c81c17f93049c0ab96cd4794da50272020-11-01T00:00:00Zhttps://www.dovepress.com/resveratrol-inhibits-lipopolysaccharide-induced-extracellular-matrix-a-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Wenyan 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-κBGong WLi JChen WFeng FDeng YDove Medical Pressarticlediabetic nephropathyresveratrollipopolysaccharidesphingosine kinase 1sphingosine 1-phosphatenf-κbSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 13, Pp 4495-4505 (2020) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
diabetic nephropathy resveratrol lipopolysaccharide sphingosine kinase 1 sphingosine 1-phosphate nf-κb Specialties of internal medicine RC581-951 |
| spellingShingle |
diabetic nephropathy resveratrol lipopolysaccharide sphingosine kinase 1 sphingosine 1-phosphate nf-κb Specialties of internal medicine RC581-951 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 |
| 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 |
| format |
article |
| 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 |
| title |
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_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_sort |
resveratrol inhibits lipopolysaccharide-induced extracellular matrix accumulation and inflammation in rat glomerular mesangial cells by sphk1/s1p2/nf-κb pathway |
| publisher |
Dove Medical Press |
| publishDate |
2020 |
| url |
https://doaj.org/article/82c81c17f93049c0ab96cd4794da5027 |
| work_keys_str_mv |
AT gongw resveratrolinhibitslipopolysaccharideinducedextracellularmatrixaccumulationandinflammationinratglomerularmesangialcellsbysphk1s1p2nfkappabpathway AT lij resveratrolinhibitslipopolysaccharideinducedextracellularmatrixaccumulationandinflammationinratglomerularmesangialcellsbysphk1s1p2nfkappabpathway AT chenw resveratrolinhibitslipopolysaccharideinducedextracellularmatrixaccumulationandinflammationinratglomerularmesangialcellsbysphk1s1p2nfkappabpathway AT fengf resveratrolinhibitslipopolysaccharideinducedextracellularmatrixaccumulationandinflammationinratglomerularmesangialcellsbysphk1s1p2nfkappabpathway AT dengy resveratrolinhibitslipopolysaccharideinducedextracellularmatrixaccumulationandinflammationinratglomerularmesangialcellsbysphk1s1p2nfkappabpathway |
| _version_ |
1718392628345569280 |