Podocyte protection by darbepoetin: preservation of the cytoskeleton and nephrin expression
Podocyte protection by darbepoetin: preservation of the cytoskeleton and nephrin expression
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DOI：
10.1038/sj.ki.5002311
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发表时间：
2007-08-01
影响因子：
19.6
通讯作者：
Nangaku, M.
中科院分区：
文献类型：
--
作者：
Eto, N.;Wada, T.;Nangaku, M.
足细胞损伤是蛋白尿和肾小球硬化的重要原因。最近的研究表明，红细胞生成素（EPO）在缺血性肾病中具有肾保护作用。在这项研究中，我们研究了长效重组EPO类似物达贝泊苷在嘌呤霉素氨基胍诱导的肾病综合征模型中可能赋予肾保护作用的机制。达贝泊利可减少嘌呤霉素处理的大鼠的蛋白尿。这种保护作用与足细胞损伤标志物结蛋白和免疫共刺激分子B7.1的免疫组化消失以及裂膈中nephrin表达的再现相关。足细胞足突收缩和消失沿着与肌动蛋白丝重排，通过电子显微镜测定，都逆转了达贝泊胺治疗。在已被血液稀释至正常红细胞压积水平的嘌呤霉素诱导的肾病大鼠中证实了保护作用。此外，嘌呤霉素治疗大鼠足细胞培养引起肌动蛋白细胞骨架重组沿着与nephrin分布紊乱。所有这些作用在体外被达贝泊利逆转。我们的研究表明，达贝泊治疗通过对足细胞的直接作用改善足细胞损伤并减少蛋白尿。这可以通过维持肌动蛋白细胞骨架和nephrin表达来实现。
Podocyte injury is a significant contributor to proteinuria and glomerulosclerosis. Recent studies have shown a renoprotective effect of erythropoietin (EPO) during ischemic kidney disease. In this study, we examine mechanisms by which a long acting recombinant EPO analog, darbepoetin, may confer renoprotection in the puromycin aminonucleoside-induced model of nephrotic syndrome. Darbepoetin decreased the proteinuria of rats treated with puromycin. This protective effect was correlated with the immunohistochemical disappearance of the podocyte injury markers desmin and the immune costimulator molecule B7.1 with the reappearance of nephrin expression in the slit diaphragm. Podocyte foot process retraction and effacement along with actin filament rearrangement, determined by electron microscopy, were all reversed by darbepoetin treatment. The protective effects were confirmed in puromycin-induced nephrotic rats that had been hemodiluted to normal hematocrit levels. Furthermore, puromycin treatment of rat podocytes in culture caused actin cytoskeletal reorganization along with deranged nephrin distribution. All these effects in vitro were reversed by darbepoetin. Our study demonstrates that darbepoetin treatment ameliorates podocyte injury and decreases proteinuria by a direct effect on podocytes. This may be accomplished by maintenance of the actin cytoskeleton and nephrin expression.