S1P2 receptor mediates sphingosine-1-phosphate-induced fibronectin expression via MAPK signaling pathway in mesangial cells under high glucose condition

被引：46

作者：

Liu, Weihua ^{[2
]}

Lan, Tian ^{[3
]}

Xie, Xi

Huang, Kaipeng

Peng, Jing

Huang, Juan

Shen, Xiaoyan

Liu, Peiqing

Huang, Heqing ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Sch Pharmaceut Sci, Lab Pharmacol & Toxicol, Guangzhou Higher Educ Mega Ctr, Guangzhou 510006, Guangdong, Peoples R China

[2] GuangZhou Med Univ, Affiliated Hosp 2, Guangzhou Inst Cardiovasc Dis, Guangzhou 510260, Guangdong, Peoples R China

[3] Guangdong Pharmaceut Univ, Inst Vasc Biol, Guangzhou 510006, Guangdong, Peoples R China

来源：

EXPERIMENTAL CELL RESEARCH | 2012年 / 318卷 / 08期

基金：

中国国家自然科学基金;

关键词：

Diabetic nephropathy; Sphingosine-1-phosphate; Sphingosine-1-phosphate receptors; Fibronectin; Mitogen-activated protein kinase signaling pathway; PROTEIN-COUPLED RECEPTORS; SMOOTH-MUSCLE-CELLS; SPHINGOSINE; 1-PHOSPHATE; DIABETIC-NEPHROPATHY; LYSOPHOSPHOLIPID RECEPTORS; ENDOTHELIAL-CELLS; ALDOSE REDUCTASE; OXIDATIVE STRESS; RENAL INJURY; PROLIFERATION;

D O I：

10.1016/j.yexcr.2012.02.020

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Accumulation of extracellular matrix including fibronectin in mesangium is one of the major pathologic characteristics in diabetic nephropathy. In the current study, we explored role of sphingosine-1-phosphate (S1P) receptor in fibronectin expression and underlying molecular mechanism. Among five S1P receptors the mRNA level of S1P2 receptor was the most abundant in kidney of diabetic rats and mesangial cells under high glucose condition. SIP augmentation of fibronectin was significantly inhibited by S1P2 receptor antagonist JTE-013 and S1P2-siRNA. SIP-stimulated fibronectin expression was remarkably blocked by ERK1/2 inhibitor PD98059 and p38MAPK inhibitor SB203580. Phospho-ERK1/2 and phospho-p38MAPK level induced by SIP were markedly abrogated by JTE-013 and S1P2-siRNA. In conclusion, S1P2 receptor was significantly up-regulated under diabetic condition. S1P2 receptor mediated fibronectin expression through the activation of SIP-S1P2-MAPK (ERK1/2 and p38MAPK) axis in mesangial cells under high glucose condition, suggesting that it might be a potential therapeutic target for diabetic nephropathy treatment. (C) 2012 Elsevier Inc. All rights reserved.

引用

页码：936 / 943

页数：8

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