Increased Expression of Toll-Like Receptor 2 in Rat Diabetic Nephropathy
Increased Expression of Toll-Like Receptor 2 in Rat Diabetic Nephropathy
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DOI：
10.1159/000317023
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发表时间：
2010-01-01
影响因子：
4.2
通讯作者：
Yu, Xueqing
中科院分区：
文献类型：
--
作者：
Li, Fanglin;Yang, Niansheng;Yu, Xueqing
背景/目的：炎症参与糖尿病肾病（DN）的发病机制。本研究探讨了Toll样受体2（TLR 2）在大鼠DN模型肾损伤进展中的作用。方法：采用链脲佐菌素（STZ）诱导DN大鼠模型，分别于第2、4、8周处死大鼠。检测功能和病理标志物、炎症浸润、TLR 2、MCP-1、MyD 88、HSP 70、HMG B1的表达和NF-κ B B的活化。体外实验观察葡萄糖对肾小管上皮细胞TLR 2表达的影响。结果如下：糖尿病大鼠肾脏TLR 2 mRNA和蛋白表达显著上调（p < 0.01），与肾脏MyD 88和MCP-1表达增加、NF-κ B活化和巨噬细胞浸润有关。TLRs的内源性配体HSP 70和HMGB 1在糖尿病大鼠肾脏中的表达也显著上调。在DN患者肾活检组织中，TLR 2在肾小球和肾小管均有明显表达。体外实验结果显示高糖诱导NRK-52 E细胞TLR 2 mRNA的表达（p < 0.01）。结论：DN患者肾脏TLR 2表达增强与炎症浸润有关。版权所有（C）2010 S. Karger AG，巴塞尔
Background/Aims: Inflammation is implicated in the pathogenesis of diabetic nephropathy (DN). This study examined the role of Toll-like receptor 2 (TLR2) in the progression of renal injury in a model of rat DN. Methods: DN was induced by intravenous injection of streptozotocin and rats were sacrificed at week 2, 4 and 8. Functional and pathologic markers, inflammatory infiltration, expression of TLR2, MCP-1, MyD88, HSP70, HMGB1 and activation of NF-kappa B were assessed. The effects of glucose on the expression of TLR2 by renal tubular epithelial cells were also examined in vitro. Results: The expression of TLR2 mRNA and protein level was significantly upregulated in the kidneys of diabetic rats (p < 0.01), which was associated with increased renal expression of MyD88 and MCP-1, activation of NF-kappa B and infiltration of macrophages. The expression of HSP70 and HMGB1, endogenous ligands of TLRs, was also significantly upregulated in the kidneys of diabetic rats. In human renal biopsy of DN, there was prominent expression of TLR2 in both the glomeruli and tubulointerstitium. In vitro study showed that high glucose induced the expression of TLR2 mRNA by NRK-52E cells (p < 0.01). Conclusions: Enhanced renal expression of TLR2 is associated with inflammatory infiltration in DN. Copyright (C) 2010 S. Karger AG, Basel