Overexpression of Toll-like receptor 8 correlates with the progression of podocyte injury in murine autoimmune glomerulonephritis.
Overexpression of Toll-like receptor 8 correlates with the progression of podocyte injury in murine autoimmune glomerulonephritis.
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DOI：
10.1038/srep07290
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发表时间：
2014-12-03
影响因子：
4.6
通讯作者：
Kon Y
中科院分区：
文献类型：
--
作者：
Kimura J;Ichii O;Miyazono K;Nakamura T;Horino T;Otsuka-Kanazawa S;Kon Y
Toll样受体（TLR）家族成员作为病原体传感器，参与局部自身免疫反应。本研究通过分析BXSB/MpJ-Yaa（BXSB-Yaa）狼疮模型小鼠发现肾小球损伤与TLR表达之间的相关性。在离体肾小球中，BXSB-Yaa小鼠中几种TLR的mRNA表达高于健康对照BXSB小鼠。特别是，Tlr 8及其下游细胞因子的表达显著增加。在小鼠肾脏中，TLR 8蛋白和mRNA定位于足细胞，并且BXSB-Yaa小鼠的肾小球中TLR 8蛋白表达高于BXSB小鼠。在BXSB-Yaa小鼠中，肾小球Tlr 8 mRNA水平与肾小球足细胞功能标志物（Nphs 1，Nphs 2和Synpo）水平呈负相关，与尿白蛋白水平呈正相关。此外，BXSB-Yaa小鼠的肾小球和血清miR-21（一种假定的TLR 8 microRNA配体）水平高于BXSB小鼠。BXSB-Yaa小鼠尿中Tlr 8 mRNA水平也高于BXSB小鼠。总之，TLR 8的过度表达与肾小球肾炎足细胞损伤的进展相关。因此，尿Tlr 8 mRNA水平的改变可能反映足细胞损伤。
Members of the Toll-like receptor (TLR) family serve as pathogen sensors and participate in local autoimmune responses. This study found a correlation between glomerular injury and TLR expression by analysing BXSB/MpJ-Yaa (BXSB-Yaa) lupus model mice. In isolated glomeruli, the mRNA expression of several TLRs was higher in BXSB-Yaa mice than in healthy control BXSB mice. In particular, the expression of Tlr8 and its downstream cytokines was markedly increased. In mouse kidneys, TLR8 protein and mRNA localized to podocytes, and TLR8 protein expression in the glomerulus was higher in BXSB-Yaa mice than in BXSB mice. In BXSB-Yaa mice, the glomerular levels of Tlr8 mRNA negatively correlated with the glomerular levels of podocyte functional markers (Nphs1, Nphs2, and Synpo) and positively correlated with urinary albumin levels. Furthermore, the glomerular and serum levels of miR-21, a putative microRNA ligand of TLR8, were higher in BXSB-Yaa mice than in BXSB mice. The urinary levels of Tlr8 mRNA were also higher in BXSB-Yaa mice than in BXSB mice. In conclusion, the overexpression of TLR8 correlates with the progression of podocyte injury in glomerulonephritis. Thus, altered levels of urinary Tlr8 mRNA might reflect podocyte injury.
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影响因子：
4.4
作者：
Muzio, M;Bosisio, D;Mantovani, A
通讯作者：
Mantovani, A
影响因子：
4.4
作者：
Andersen-Nissen, Erica;Hawn, Thomas R.;Aderem, Alan
通讯作者：
Aderem, Alan
DOI：
10.1073/pnas.1209414109
发表时间：
2012-07-31
影响因子：
11.1
作者：
Fabbri, Muller;Paone, Alessio;Croce, Carlo M.
通讯作者：
Croce, Carlo M.
影响因子：
56.9
作者：
Peng, GY;Guo, Z;Wang, RF
通讯作者：
Wang, RF
影响因子：
4.6
作者：
Mersmann, Jan;Iskandar, Franziska;Koch, Alexander
通讯作者：
Koch, Alexander