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

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单位: [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
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关键词: SDF-1 alpha TGF-beta Mesangial cells Fibronectin CXCR4

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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.

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出版当年[2012]版:
大类 | 2 区 医学
小类 | 3 区 肿瘤学 4 区 细胞生物学
最新[2025]版:
大类 | 3 区 生物学
小类 | 4 区 细胞生物学 4 区 肿瘤学
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出版当年[2011]版:
Q2 CELL BIOLOGY Q2 ONCOLOGY
最新[2023]版:
Q2 ONCOLOGY Q3 CELL BIOLOGY

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第一作者单位: [1]HUST, Tongji Hosp, Tongji Med Coll, Dept Internal Med,Div Endocrinol, Wuhan 430030, Hubei Province, Peoples R China
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通讯机构: [1]HUST, Tongji Hosp, Tongji Med Coll, Dept Internal Med,Div Endocrinol, Wuhan 430030, Hubei Province, Peoples R China [*1]HUST, Tongji Hosp, Tongji Med Coll, Dept Internal Med,Div Endocrinol, 1095 Jiefang Rd, Wuhan 430030, Hubei Province, Peoples R China
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