The monocyte chemoattractant protein-1/cognate CC chemokine receptor 2 system affects cell motility in cultured human podocytes
The monocyte chemoattractant protein-1/cognate CC chemokine receptor 2 system affects cell motility in cultured human podocytes
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DOI：
10.2353/ajpath.2007.070398
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发表时间：
2007-12-01
影响因子：
6
通讯作者：
Gruden, Gabriella
中科院分区：
文献类型：
--
作者：
Burt, Davina;Salvidio, Gennaro;Gruden, Gabriella
在新月体肾小球肾炎 (GN) 中，单核细胞趋化蛋白 1 (MCP-1) 在肾小球内过度表达，MCP-1 阻断具有肾脏保护作用。成体足细胞处于静止状态，但在新月体肾小球肾炎中描述了迁移/增殖表型的获得，并与新月体形成有关。同源 CC 趋化因子受体 2 (CCR2)，即 MCP-1 受体，除单核细胞外还由其他细胞类型表达，并且与细胞增殖和迁移有关。我们研究了 MCP-1 与 CCR2 的结合是否可以诱导培养的足细胞的迁移/增殖反应。 MCP-1 与 CCR2 的结合以浓度依赖性方式增强足细胞趋化性/趋触性，并对细胞增殖有一定影响。 CCR2 阻断会延迟受伤足细胞单层的闭合，并且 CCR2 在伤口边缘过度表达，表明 CCR2 在驱动足细胞迁移中发挥作用。对新月体 GN 患者肾活检的免疫组织化学分析表明，足细胞和细胞新月体中均表达 CCR2，证实了我们体外研究结果的临床相关性。总之，MCP-1/CCR2 系统在足细胞中功能活跃，可能与新月体肾小球肾炎和其他肾小球疾病中足细胞损伤引发的迁移事件有关。
In crescentic glomerulonephritis (GN), monocyte chemoattractant protein-1 (MCP-1) is overexpressed within the glomeruli, and MCP-1 blockade has renoprotective effects. Adult podocytes are in a quiescent state, but acquisition of a migratory/proliferative phenotype has been described in crescentic GN and implicated in crescent formation. The cognate CC chemokine receptor 2 (CCR2), the MCP-1 receptor, is expressed by other cell types besides monocytes and has been implicated in both cell proliferation and migration. We investigated whether MCP-1 binding to CCR2 can induce a migratory/proliferative response in cultured podocytes. MCP-1 binding to CCR2 enhanced podocyte chemotaxis/haptotaxis in a concentration-dependent manner and had a modest effect on cell proliferation. Closure of a wounded podocyte monolayer was delayed by CCR2 blockade, and CCR2 was overexpressed at the wound edge, suggesting a role for CCR2 in driving podocyte migration. Inummohistochemical analysis of kidney biopsies from patients with crescentic GN demonstrated CCR2 expression in both podocytes and cellular crescents, confirming the clinical relevance of our in vitro findings. in conclusion, the MCP-1/CCR2 system is functionally active in podocytes and may be implicated in the migratory events triggered by podocyte injury in crescentic GN and other glomerular diseases.