Effect of the monocyte chemoattractant protein-1/CC chemokine receptor 2 system on nephrin expression in streptozotocin-treated mice and human cultured podocytes.
Effect of the monocyte chemoattractant protein-1/CC chemokine receptor 2 system on nephrin expression in streptozotocin-treated mice and human cultured podocytes.
复制标题
作者：
Tarabra E;Giunti S;Barutta F;Salvidio G;Burt D;Deferrari G;Gambino R;Vergola D;Pinach S;Perin PC;Camussi G;Gruden G
单核细胞趋化蛋白-1（MCP-1）是一种与CC趋化因子受体2（CCR 2）结合并促进单核细胞浸润的趋化因子，与糖尿病肾病的发病机制有关。为了评估MCP-1/CCR 2系统在糖尿病蛋白尿发病机制中的潜在相关性，我们在体外研究了MCP-1与CCR 2受体的结合是否调节培养足细胞中nephrin的表达。此外，我们在体内研究了糖尿病肾病患者肾活检中肾小球CCR 2表达是否改变，以及MCP-1缺乏是否影响实验性糖尿病患者的蛋白尿和nephrin表达。通过免疫荧光和实时荧光PCR检测rh-MCP-1诱导的人足细胞nephrin的表达。采用免疫组化方法研究了10例显性肾病患者和8例对照组患者的肾切片中肾小球CCR 2的表达。野生型和MCP-1基因敲除小鼠均用链脲佐菌素制成糖尿病小鼠。糖尿病发病后10周，蛋白尿和nephrin，synaptopodin，和zonula occludens-1的表达通过免疫荧光和免疫印迹进行了检查。在人足细胞中，MCP-1与CCR 2受体的结合通过Rho依赖性机制诱导nephrin mRNA和蛋白质表达的显著降低。MCP-1受体CCR 2在显性肾病患者的肾小球足细胞中过表达。在实验性糖尿病中，MCP-1在肾小球内过表达，MCP-1的缺乏减少了白蛋白尿和nephrin和synaptopodin的下调。这些发现表明MCP-1/CCR 2系统可能与糖尿病蛋白尿的发病机制有关。
Monocyte chemoattractant protein-1 (MCP-1), a chemokine binding to the CC chemokine receptor 2 (CCR2) and promoting monocyte infiltration, has been implicated in the pathogenesis of diabetic nephropathy. To assess the potential relevance of the MCP-1/CCR2 system in the pathogenesis of diabetic proteinuria, we studied in vitro if MCP-1 binding to the CCR2 receptor modulates nephrin expression in cultured podocytes. Moreover, we investigated in vivo if glomerular CCR2 expression is altered in kidney biopsies from patients with diabetic nephropathy and whether lack of MCP-1 affects proteinuria and expression of nephrin in experimental diabetes. Expression of nephrin was assessed in human podocytes exposed to rh-MCP-1 by immunofluorescence and real-time PCR. Glomerular CCR2 expression was studied in 10 kidney sections from patients with overt nephropathy and eight control subjects by immunohistochemistry. Both wild-type and MCP-1 knockout mice were made diabetic with streptozotocin. Ten weeks after the onset of diabetes, albuminuria and expression of nephrin, synaptopodin, and zonula occludens-1 were examined by immunofluorescence and immunoblotting. In human podocytes, MCP-1 binding to the CCR2 receptor induced a significant reduction in nephrin both mRNA and protein expression via a Rho-dependent mechanism. The MCP-1 receptor, CCR2, was overexpressed in the glomerular podocytes of patients with overt nephropathy. In experimental diabetes, MCP-1 was overexpressed within the glomeruli and the absence of MCP-1 reduced both albuminuria and downregulation of nephrin and synaptopodin. These findings suggest that the MCP-1/CCR2 system may be relevant in the pathogenesis of proteinuria in diabetes.
登录
查看更多内容
影响因子：
13.6
作者：
Kalluri, Raghu
通讯作者：
Kalluri, Raghu
影响因子：
19.6
作者：
Li, J. J.;Kwak, S. J.;Kang, S-W
通讯作者：
Kang, S-W
影响因子：
6
作者：
Burt, Davina;Salvidio, Gennaro;Gruden, Gabriella
通讯作者：
Gruden, Gabriella
影响因子：
4.7
作者：
Banisadr, G;Quéraud-Lesaux, F;Parsadaniantz, SM
通讯作者：
Parsadaniantz, SM
影响因子：
13.6
作者：
Bussolati, B;Deregibus, MC;Camussi, G
通讯作者：
Camussi, G