HGF protects rat mesangial cells from high-glucose-mediated oxidative stress
HGF protects rat mesangial cells from high-glucose-mediated oxidative stress
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HGF 保护大鼠系膜细胞免受高葡萄糖介导的氧化应激
DOI：
10.1159/000097368
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发表时间：
2006-01-01
影响因子：
4.2
通讯作者：
Zhang, Nong
中科院分区：
文献类型：
--
作者：
Li, Hui;Jiang, Tao;Zhang, Nong
背景：氧化应激被认为是糖尿病肾病的一个常见发病因素。最近的研究表明肝细胞生长因子（HGF）是一种抗氧化生长因子，因此，其在糖尿病肾病中的肾脏保护作用可能与抗氧化机制有关。本研究旨在观察肝细胞生长因子（HGF）对高糖诱导的大鼠肾小球系膜细胞（RMC）氧化应激的保护作用，并探讨其相关机制。研究方法：在不存在或存在HGF（20 ng/ml）和c-met抑制剂SU 11274（5 μ M）的情况下，将RMC在5.6 mM（NG）或30 mM（HG）葡萄糖中培养24小时。结果：HG中c-met表达明显增加。HG中观察到氧化应激增强，表现为活性氧和丙二醛水平升高和谷胱甘肽水平降低，HGF可显著减弱氧化应激。HGF还通过抑制USF与GCLC启动子负调控区的结合，抑制HG诱导的p22（phox）和醛糖还原酶上调，并阻止HG还原的谷氨酸-半胱氨酸连接酶催化亚基（GCLC）表达。HG降低的RMC中葡萄糖-6-磷酸脱氢酶活性和表达被HGF拯救。结论：HGF可作为抗氧化因子，通过增强ROS清除和抑制ROS产生来对抗HG介导的氧化应激。版权所有（c）2006 S. Karger AG，巴塞尔
Background: Oxidative stress has been considered to be a common pathogenetic factor of diabetic nephropathy. Recent observations suggested that hepatocyte growth factor (HGF) was an antioxidant growth factor; thus, its renoprotective effects in diabetic nephropathy might be related to antioxidant mechanism. The aim of the present study was to evaluate whether HGF could prevent rat mesangial cells (RMC) from high-glucose-mediated oxidative stress and explore its relevant mechanism. Methods: RMC were cultured in 5.6 mM (NG) or 30 mM (HG) glucose in the absence or presence of HGF (20 ng/ml) and c-met inhibitor SU11274 (5 mu M) for 24 h. Results: c-met expression in HG was markedly increased. Enhanced oxidative stress was observed in HG as evidenced by elevated reactive oxygen species and malondialdehyde levels and decreased glutathione level, which was markedly attenuated by HGF. HGF also inhibited HG-induced p22(phox) and aldose reductase upregulation and prevented HG-reduced glutamate-cysteine ligase catalytic subunit (GCLC) expression through inhibiting USF binding to negative regulatory region of GCLC promoter. Reduced glucose-6-phosphate dehydrogenase activity and expression in RMC by HG was rescued by HGF. Conclusion: HGF could function as an antioxidant factor and protect against HG-mediated oxidative stress by enhancing ROS scavenging and suppressing ROS production. Copyright (c) 2006 S. Karger AG, Basel