SDF-1α reduces fibronectin expression in rat mesangial cells induced by TGF-β1 and high glucose through PI3K/Akt pathway

被引：31

作者：

Zhang, Dan ^{[1
]}

Shao, Shiying ^{[1
]}

Shuai, Hongxia ^{[1
]}

Ding, Yunchuan ^{[1
]}

Shi, Wei ^{[1
]}

Wang, Daowen ^{[2
]}

Yu, Xuefeng ^{[1
]}

机构：

[1] HUST, Tongji Hosp, Tongji Med Coll, Dept Internal Med,Div Endocrinol, Wuhan 430030, Hubei Province, Peoples R China

[2] HUST, Tongji Hosp, Tongji Med Coll, Dept Internal Med,Div Cardiovasc Dis, Wuhan 430030, Hubei Province, Peoples R China

来源：

EXPERIMENTAL CELL RESEARCH | 2013年 / 319卷 / 12期

基金：

中国国家自然科学基金;

关键词：

SDF-1; alpha; TGF-beta; Mesangial cells; Fibronectin; CXCR4; GROWTH-FACTOR-BETA; TGF-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1; INDUCED APOPTOSIS; EXTRACELLULAR-MATRIX; DIABETIC-NEPHROPATHY; SDF-1-CXCR4; AXIS; ACTIVATION; SMAD3; AKT;

D O I：

10.1016/j.yexcr.2013.03.030

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Stromal cell-derived factor-1 (SDF-1) is a chemokine and plays an important role in cell migration, whereas its role in diabetic nephropathy has not been illustrated distinctly. We hypothesized that SDF-1 alpha may have an effect on extracellular matrix (ECM) accumulations in mesangial cells exposed to transforming growth factor-beta 1 (TGF-beta 1) or high glucose in vitro. The exogenous SDF-1 alpha was added into rat mesangial cells incubated with TGF-beta 1 or high glucose in the medium. The expression of fibronectin (FN) was quantitated by real-time RT-PCR, and the change of Akt and Smad3 measured by western blotting. SDF-1 alpha, its receptor C-X-C chemokine receptor type 4 (CXCR4) and FN mRNA were expressed in rat mesangial cells. Both TGF-beta 1 and high glucose raised the mRNA expressions of CXCR4 and FN in the cells. SDF-1 alpha inhibited the elevated FN mRNA expression induced by TGF-beta 1 and high glucose through CXCR4 and PI3K/Akt signaling pathway, as the effect of SDF-1 alpha was reversed by CXCR4 antagonist AMD3100 and PI3K inhibitor LY294002. Correspondingly, TGF-beta 1 induced Smad3 phosphorylation was suppressed when PI3K/Akt signaling pathway was activated by SDF-1 alpha. Based on these findings, we conclude that SDF-1 alpha ameliorates TGF-beta 1/high glucose induced ECM accumulations in mesangial cells, which may mediate through PI3K/Akt pathway. This novel mechanism may bring a new insight to our understandings of diabetic nephropathy. (C) 2013 Elsevier Inc. All rights reserved.

引用

页码：1796 / 1803

页数：8

共 42 条

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