Sulforaphane attenuation of experimental diabetic nephropathy involves GSK-3 beta/Fyn/Nrf2 signaling pathway
Sulforaphane attenuation of experimental diabetic nephropathy involves GSK-3 beta/Fyn/Nrf2 signaling pathway
复制标题
萝卜硫素对实验性糖尿病肾病的减弱作用涉及GSK-3 beta/Fyn/Nrf2信号通路
DOI：
10.1016/j.jnutbio.2014.12.008
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发表时间：
2015-06-01
影响因子：
5.6
通讯作者：
Li, Hui
中科院分区：
文献类型：
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作者：
Shang, Guoguo;Tang, Xinjun;Li, Hui
萝卜硫素（Sulforaphane，SFN）是十字花科蔬菜的生物活性成分，是一种有效的间接抗氧化剂。氧化应激和糖原合成酶激酶3 β（Glycogen synthase kinase 3 beta，GSK 3 beta）的激活是糖尿病肾病（diabetic nephropathy，DN）发病的两个主要因素。在这里，我们研究了SFN是否以及如何影响体内和体外DN实验模型中的GSK 3 β。SFN治疗可明显抑制糖尿病肾组织中尿白蛋白排泄、基质扩张、转化生长因子β 1表达、纤维连接蛋白和IV型胶原沉积的增加。同时，SFN治疗的糖尿病大鼠中氧化损伤的指标8-氧代-脱氧鸟苷的水平显著降低，GSK-3 β/Fyn轴的活性显著降低，Nrf 2信号传导明显活化。类似地，SFN的抗纤维化作用，平行于增强的抑制GSK 3 β和Fyn/Nrf 2核输出/输入的Ser 9-磷酸化，在暴露于高葡萄糖的培养大鼠肾小球系膜细胞（RMC）中观察到。SFN对高糖刺激的RMC的有益作用被GSK 3 β的过表达所消除，同时被氯化锂（一种众所周知的GSK 3 β抑制剂）拯救。综上所述，我们的研究结果表明，SFN改善实验性糖尿病肾病，至少部分，通过GSK 3 β/Fyn/Nrf 2信号通路。(C)2015 Elsevier Inc. All rights reserved.
Sulforaphane (SFN), the bioactive component of cruciferous vegetables, is a potent indirect antioxidant Oxidative stress and activation of glycogen synthase kinase 3beta (GSK3 beta) are two major contributors to the pathogenesis of diabetic nephropathy (DN). Here, we investigated whether and how SFN affected GSK3 beta in experimental models of DN in vivo and in vitro. SFN treatment obviously prevented the increase in urine albumin excretion, matrix expansion, transforming growth factor-beta 1 expression, fibronectin and type IV collagen deposition in the diabetic kidney. Simultaneously, the level of 8-oxo-deoxyguanosine, an indicator of oxidative damage, was markedly lowered in SFN-treated diabetic rats, together with a significant reduction in activity of the GSK-3 beta/Fyn axis and an evident activation of Nrf2 signaling. Similarly, antifibrotic effects of SFN, parallel to enhanced inhibitory Ser9-phosphorylation of GSK3 beta and Fyn/Nrf2 nuclear export/import, were observed in the cultured rat mesangial cells (RMC) exposed to high glucose. The salutary effects of SFN on high-glucose-stimulated RMC were abolished by overexpression of GSK3 beta while being rescued by lithium chloride, a well-known GSK3 beta inhibitor. Taken together, our findings suggested that SFN ameliorated experimental diabetic nephropathy, at least in part, via GSK3 beta/Fyn/Nrf2 signaling pathway. (C) 2015 Elsevier Inc. All rights reserved.