Predictive significance of kidney myeloid-related protein 8 expression in patients with obesity- or type 2 diabetes-associated kidney diseases.
Predictive significance of kidney myeloid-related protein 8 expression in patients with obesity- or type 2 diabetes-associated kidney diseases.
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DOI：
10.1371/journal.pone.0088942
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Mukoyama M
中科院分区：
文献类型：
--
作者：
Kuwabara T;Mori K;Kasahara M;Yokoi H;Imamaki H;Ishii A;Koga K;Sugawara A;Yasuno S;Ueshima K;Morikawa T;Konishi Y;Imanishi M;Nishiyama A;Nakao K;Mukoyama M
我们报道了Toll样受体4（TLR4）及其内源性配体之一髓样相关蛋白8（MRP8或S100A8）在小鼠糖尿病肾病的进展中发挥重要作用。本研究的目的是评估肥胖或 2 型糖尿病相关肾脏疾病患者肾脏 MRP8 表达的意义。在糖尿病、肥胖或对照受试者中，通过实时 RT-PCR 和免疫组织化学测定肾活检样本中的 MRP8 mRNA 和蛋白表达水平（分别为 n =28 和 65），并分析它们与基线和预后参数的关联。使用巨噬细胞检查了 MRP8 对促炎基因表达的影响。与对照组相比，肥胖或糖尿病组的肾脏 MRP8 基因和蛋白表达水平升高。在所有受试者中，通过单变量线性回归分析，基线时肾小球MRP8阳性细胞计数和肾小管间质MRP8阳性面积均分别与各种已知的糖尿病肾病危险因素（如收缩压、蛋白尿和血清肌酐）相关，而且与肾小球硬化和肾小管间质纤维化的程度相关。通过多变量分析检查预测一年后尿蛋白水平的独立因素，包括肾小球MRP8阳性细胞计数（β = 0.59，P<0.001）、蛋白尿（β = 0.37，P = 0.002）和收缩压（β = 0.21， P = 0.04）在基线，调整已知的风险因素后。在 CD68 阳性巨噬细胞和萎缩小管中观察到 MRP8 蛋白表达。在培养的小鼠巨噬细胞中，MRP8 蛋白诱导促炎细胞因子表达，并以 TLR4 依赖性方式触发 MRP8 的自诱导。肾小球 MRP8 表达似乎与肥胖或 2 型糖尿病患者的蛋白尿进展相关，可能是通过 TLR4 信号传导诱导巨噬细胞炎症变化所致。
We have reported that toll-like receptor 4 (TLR4) and one of its endogenous ligands, myeloid-related protein 8 (MRP8 or S100A8), play an important role in the progression of diabetic nephropathy in mice. The aim of this study was to evaluate significance of kidney MRP8 expression in patients with obesity- or type 2 diabetes-associated kidney diseases. In diabetic, obese or control subjects, MRP8 mRNA and protein expression levels in renal biopsy samples were determined by real-time RT-PCR and immunohistochemistry (n = 28 and 65, respectively), and their associations with baseline and prognostic parameters were analyzed. Effects of MRP8 upon pro-inflammatory gene expressions were examined using macrophages. Kidney MRP8 gene and protein expression levels were elevated in obese or diabetic groups compared to control group. Among all subjects, by univariate linear regression analysis, glomerular MRP8-positive cell count and tubulointerstitial MRP8-positive area at baseline were both, respectively, correlated not only with various known risk factors for diabetic nephropathy (such as systolic blood pressure, proteinuria and serum creatinine) but also with extent of glomerulosclerosis and tubulointerstitial fibrosis. Independent factors predicting urinary protein levels a year later were examined by multivariate analysis, and they included glomerular MRP8-positive cell count (β = 0.59, P<0.001), proteinuria (β = 0.37, P = 0.002) and systolic blood pressure (β = 0.21, P = 0.04) at baseline, after adjustment for known risk factors. MRP8 protein expression was observed in CD68-positive macrophages and atrophic tubules. In cultured mouse macrophages, MRP8 protein induced proinflammatory cytokine expressions and also triggered auto-induction of MRP8 in a TLR4-dependent manner. Glomerular MRP8 expression appears to be associated with progression of proteinuria in obese or type 2 diabetic patients, possibly by inducing inflammatory changes in macrophages through TLR4 signaling.
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影响因子：
37.8
作者：
Croce K;Gao H;Wang Y;Mooroka T;Sakuma M;Shi C;Sukhova GK;Packard RR;Hogg N;Libby P;Simon DI
通讯作者：
Simon DI
影响因子：
--
作者：
Ravid, M;Brosh, D;Rachmani, R
通讯作者：
Rachmani, R
影响因子：
19.6
作者：
Kuwabara, Takashige;Mori, Kiyoshi;Nakao, Kazuwa
通讯作者：
Nakao, Kazuwa
影响因子：
6.1
作者：
Nishiyama, Akira;Konishi, Yoshio;Imanishi, Masahito
通讯作者：
Imanishi, Masahito
影响因子：
29
作者：
Nagareddy PR;Murphy AJ;Stirzaker RA;Hu Y;Yu S;Miller RG;Ramkhelawon B;Distel E;Westerterp M;Huang LS;Schmidt AM;Orchard TJ;Fisher EA;Tall AR;Goldberg IJ
通讯作者：
Goldberg IJ