Fli-1 transcription factor affects glomerulonephritis development by regulating expression of monocyte chemoattractant protein-1 in endothelial cells in the kidney.
Fli-1 transcription factor affects glomerulonephritis development by regulating expression of monocyte chemoattractant protein-1 in endothelial cells in the kidney.
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DOI：
10.1016/j.clim.2012.09.006
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发表时间：
2012-12
期刊：
影响因子：
--
通讯作者：
Zhang XK
中科院分区：
文献类型：
--
作者：
Suzuki E;Karam E;Williams S;Watson DK;Gilkeson G;Zhang XK
转录因子Fli-1的表达与肾小球肾炎的发生有关。Fli-1杂合基因敲除（Fli 1 +/−）NZM 2410小鼠，一种狼疮小鼠模型，具有显著改善的存活率和减少的肾小球肾炎。在这项研究中，我们发现Fli-1+/− NZM 2410小鼠肾脏中浸润的炎症细胞显著减少。Fli-1+/− NZM 2410小鼠肾脏中单核细胞趋化蛋白-1（MCP-1）的表达显著降低。从Fli-1+/− NZM 2410小鼠肾脏分离的原代内皮细胞产生的MCP-1显著减少。在用特异性Fli-1 siRNA转染的内皮细胞中，与用阴性对照siRNA转染的细胞相比，MCP-1的产生显著降低。通过染色质免疫沉淀（ChIP）实验，进一步证明Fli-1与MCP-1基因启动子直接结合。我们的数据表明Fli-1通过调节炎症趋化因子MCP-1的表达和NZM 2410小鼠肾脏中的炎症细胞浸润来影响肾小球肾炎的发展。
Expression of transcription factor Fli-1 is implicated in the development of glomerulonephritis. Fli-1 heterozygous knockout (Fli1+/−) NZM2410 mice, a murine model of lupus, had significantly improved survival and reduced glomerulonephritis. In this study, we found that infiltrated inflammatory cells were significantly decreased in the kidneys from Fli-1+/− NZM2410 mice. The expression of Monocyte chemoattractant protein-1 (MCP-1) was significantly decreased in kidneys from Fli-1+/− NZM2410 mice. The primary endothelial cells isolated from the kidneys of Fli-1+/− NZM2410 mice produced significantly less MCP-1. In endothelial cells transfected with specific Fli-1 siRNA the production of MCP-1 was significantly reduced compared to cells transfected with negative control siRNA. By Chromatin Immunoprecipitation (ChIP) assay, we further demonstrated that Fli-1 directly binds to the promoter of the MCP-1 gene. Our data indicate that Fli-1 impacts glomerulonephritis development by regulating expression of inflammatory chemokine MCP-1 and inflammatory cell infiltration in the kidneys in the NZM2410 mice.
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影响因子：
4.4
作者：
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通讯作者：
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DOI：
10.1016/j.bbrc.2008.11.043
发表时间：
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影响因子：
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DOI：
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发表时间：
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影响因子：
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作者：
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影响因子：
10.5
作者：
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