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.
基金:
National Natural Science Foundation of China [30772207]
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
通讯作者:
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
推荐引用方式(GB/T 7714):
Zhang Dan,Shao Shiying,Shuai Hongxia,et al.SDF-1α reduces fibronectin expression in rat mesangial cells induced by TGF-β1 and high glucose through PI3K/Akt pathway[J].EXPERIMENTAL CELL RESEARCH.2013,319(12):1796-1803.doi:10.1016/j.yexcr.2013.03.030.
APA:
Zhang, Dan,Shao, Shiying,Shuai, Hongxia,Ding, Yunchuan,Shi, Wei...&Yu, Xuefeng.(2013).SDF-1α reduces fibronectin expression in rat mesangial cells induced by TGF-β1 and high glucose through PI3K/Akt pathway.EXPERIMENTAL CELL RESEARCH,319,(12)
MLA:
Zhang, Dan,et al."SDF-1α reduces fibronectin expression in rat mesangial cells induced by TGF-β1 and high glucose through PI3K/Akt pathway".EXPERIMENTAL CELL RESEARCH 319..12(2013):1796-1803