PDF(Pubmed)
Abstract：
Investigating the role of podocytes in proteinuric disease is imperative to address the increasing global burden of chronic kidney disease (CKD). Studies strongly implicate increased levels of monocyte chemoattractant protein-1 (MCP-1/CCL2) in proteinuric CKD. Since podocytes express the receptor for MCP-1 (i.e., CCR2), we hypothesized that podocyte-specific MCP-1 production in response to stimuli could activate its receptor in an autocrine manner, leading to further podocyte injury. To test this hypothesis, we generated podocyte-specific MCP-1 knockout mice (Podo-Mcp-1fl/fl) and exposed them to proteinuric injury induced by either angiotensin II (Ang II; 1.5 mg/kg/d, osmotic minipump) or Adriamycin (Adr; 18 mg/kg, intravenous bolus). At baseline, there were no between-group differences in body weight, histology, albuminuria, and podocyte markers. After 28 days, there were no between-group differences in survival, change in body weight, albuminuria, kidney function, glomerular injury, and tubulointerstitial fibrosis. The lack of protection in the knockout mice suggests that podocyte-specific MCP-1 production is not a major contributor to either Ang II- or Adr-induced glomerular disease, implicating that another cell type is the source of pathogenic MCP-1 production in CKD.
摘要：
研究足细胞在蛋白尿疾病中的作用对于解决慢性肾脏病（CKD）日益增加的全球负担至关重要。研究强烈暗示蛋白尿CKD中单核细胞趋化蛋白-1(MCP-1/CCL2)水平升高。由于足细胞表达MCP-1的受体(即，CCR2),我们假设足细胞特异性MCP-1的产生响应刺激可以激活其受体以自分泌的方式，导致足细胞进一步损伤.为了检验这个假设，我们产生了足细胞特异性MCP-1敲除小鼠（Podo-Mcp-1fl/fl），并将其暴露于血管紧张素II（AngII；1.5mg/kg/d，渗透微型泵）或阿霉素（Adr；18mg/kg，静脉推注)。在基线,体重没有组间差异，组织学,白蛋白尿,和足细胞标记。28天后,两组之间的生存率没有差异，体重的变化,白蛋白尿,肾功能,肾小球损伤,和肾小管间质纤维化。基因敲除小鼠缺乏保护表明足细胞特异性MCP-1的产生不是AngII或Adr诱导的肾小球疾病的主要原因。暗示另一种细胞类型是CKD中致病性MCP-1产生的来源。
