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

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

Original Article | Updated：2023-05-25

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- Inhibitory Effect of Resveratrol on LPS-Induced Glomerular Mesangial Cells Proliferation and TGF-β1 Expression via Sphingosine Kinase 1 Pathway
- Chinese Journal of Integrative Medicine Vol. 29, Issue 6, Pages: 500-507(2023)
- Affiliations：
  
  1.Department of Pharmacy, the Third Affiliated Hospital of Southern Medical University, Guangzhou (510630), China
  2.Department of Cardiology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou (310000), China
- Author bio：
  
  Prof. DENG Yan-hui, E-mail: shiningdyh@sina.com
- Funds：
- DOI：10.1007/s11655-022-3530-y
  CLC：
- Published：2023-06，
  
  Published Online：08 March 2022，
  
  Accepted：08 October 2021
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FENG Fu-zhen, GONG Wen-yan, LI Si-yun, et al. Inhibitory Effect of Resveratrol on LPS-Induced Glomerular Mesangial Cells Proliferation and TGF-β1 Expression via Sphingosine Kinase 1 Pathway. [J]. Chinese Journal of Integrative Medicine 29(6):500-507(2023)
DOI：

FENG Fu-zhen, GONG Wen-yan, LI Si-yun, et al. Inhibitory Effect of Resveratrol on LPS-Induced Glomerular Mesangial Cells Proliferation and TGF-β1 Expression via Sphingosine Kinase 1 Pathway. [J]. Chinese Journal of Integrative Medicine 29(6):500-507(2023) DOI： 10.1007/s11655-022-3530-y.

摘要

目的:

2

利用脂多糖(lipopolysaccharide

LPS)诱导的肾小球系膜细胞(glomerular mesangial cells

GMCs)模型

探讨白藜芦醇(resveratrol

RSV)影响鞘氨醇激酶1 (sphingosine kinase 1

SphK1)信号通路及其下游分子激活蛋白1(activator protein 1

AP-1)和转化生长因子-β1(transformation growth factor-β1

TGF-β1)的表达而发挥的肾脏保护作用.

方法:

2

将培养的大鼠 GMCs细胞株(HBZY-1)随机分为5组: 对照组、LPS (100 ng/mL)处理组和5、10、20 μmol/L RSV给药处理组

以SphK1抑制剂(SK-Ⅱ)作为阳性对照. 给药组GMCs先用相应浓度的RSV预处理2h

再使用LPS 处理24 h后用于后续实验. 采用3-(4

5-二甲基噻唑-2-基)-2

5-二苯基溴化四氮唑(MTT)比色法测定GMCs增殖情况

利用蛋白质印迹法(Western blot)测定GMCs中SphK1、p-c-Jun和TGF-β1蛋白表达水平

使用凝胶电泳迁移实验(EMSA)测定AP-1的DNA结合活性

采用AutoDock Vina模拟RSV与SphK1蛋白的结合方式并评估二者结合活性

使用Discovery Studio 2016进行可视化.

结果:

2

LPS能明显促进GMCs增殖

并增加SphK1、p-c-Jun和TGF-β1蛋白表达

提高AP-1的DNA结合活性(

P

<

0.05或

P

<

0.01)

而 RSV 预处理后能显著抑制这些作用

且与SK-II的抑制作用相似(

P

>

0.05). 此外

RSV与SphK1对接结合能为-8.1 kcal/mol

其与SphK1上ASP178和LEU268两个氨基酸残基形成氢键

表明二者具有较好的直接结合活性.

结论:

2

RSV抑制LPS诱导的GMCs增殖及TGF-β1表达进而延缓系膜细胞纤维化进展的作用可能不依赖于其降糖效应

而是与直接抑制SphK1通路密切相关.

Abstract

Objective:

2

To elucidate the renoprotective effect of resveratrol (RSV) on sphingosine kinase 1 (SphK1) signaling pathway and expression of its downstream molecules including activator protein 1 (AP-1) and transformation growth factor-β1 (TGF-β1) in lipopolysaccharide (LPS)-induced glomerular mesangial cells (GMCs).

Methods:

2

The rat GMCs line (HBZY-1) were cultured and randomly divided into 5 groups

including control

LPS (100 ng/mL)

and 5

10

20 μmol/L RSV-treated groups. In addition

SphK1 inhibitor (SK-Ⅱ) was used as positive control. GMCs were pretreated with RSV for 2 h and treated with LPS for another 24 h. GMCs proliferation was determined by 3-(4

5-dimethylthiazol-2-yl)-2

5-diphenyl tetrazolium bromide (MTT) assay. The proteins expression of SphK1

p-c-Jun and TGF-β1 in GMCs were detected by Western blot

and DNA-binding activity of AP-1 was performed by electrophoretic mobility shift assay (EMSA). The binding activity between RSV and SphK1 protein was detected by AutoDock Vina and visualized by Discovery Studio 2016.

Results:

2

LPS could obviously stimulate GMCs proliferation

elevate SphK1

p-c-Jun and TGF-β1 expression levels and increase the DNA-binding activity of AP-1 (

P

<

0.05 or

P

<

0.01)

whereas these effects were significantly blocked by RSV pretreatment. It was also suggested that the effect of RSV was similar to SK-Ⅱ (

P

>

0.05). Moreover

RSV exhibited good binding affinity towards SphK1

with docking scores of –8.1 kcal/moL and formed hydrogen bonds with ASP-178 and LEU-268 in SphK1.

Conclusion:

2

RSV inhibited LPS-induced GMCs proliferation and TGF-β1 expression

which may be independent of its hypoglycemic effect on preventing the development of mesangial cell fibrosis and closely related to the direct inhibition of SphK1 pathway.

关键词

Keywords

resveratrolglomerular mesangial cells proliferationsphingosine kinase 1 pathwaytransformation growth factor-β1molecular docking

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The School of Basic Medical Sciences, Hubei University of Chinese Medicine

Key Laboratory of Cosmetics Monitoring and Evaluation, State Drug Administration, Shenzhen Institute for Drug Control

Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology

Department of Hepatology, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine

The Second Clinical Medical College, Guangzhou University of Chinese Medicine

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