Department of Biomedicine, Section of Cell Biology and Anatomy, University of Aarhus, Aarhus C, Denmark.
Nephrol Dial Transplant. 2012 Aug;27(8):3156-9. doi: 10.1093/ndt/gfr794. Epub 2012 Feb 15.
The bulk of proteins filtered in the glomeruli are reabsorbed in the proximal tubule by endocytosis mediated by two multiligand receptors operating in concert, megalin and cubilin. Podocytes can also internalize protein and megalin; this was initially reported in rat proximal tubular and glomerular epithelial cells and has recently also been demonstrated in human podocytes. Cubilin, crucial for albumin reabsorption in the proximal tubule, has not been identified in glomerular epithelial cells.
In the present study, we used immunocytochemistry and reverse transcription-polymerase chain reaction on laser-captured glomeruli to demonstrate synthesis and expression of cubilin in rat and human glomeruli. In parallel experiments, the expression of cubilin was studied in cultured podocytes.
This study identifies cubilin in rat and human glomeruli according to a pattern similar to that reported for megalin. Cubilin revealed a surface expression but also intracellular expression in the podocytes.
Our findings show that the podocytes display the two endocytic receptors which are responsible for the only documented process for protein reabsorption in proximal tubule cells.
肾小球滤过的大部分蛋白质通过两种多配体受体介导的内吞作用在近端小管中被重吸收,这两种受体协同作用,即巨球蛋白和 cubilin。足细胞也可以内化蛋白质和 megalin;最初在大鼠近端肾小管和肾小球上皮细胞中报道了这一点,最近也在人足细胞中得到了证实。Cubilin 对于近端小管中白蛋白的重吸收至关重要,但尚未在肾小球上皮细胞中鉴定出来。
在本研究中,我们使用激光捕获肾小球上的免疫细胞化学和逆转录聚合酶链反应来证明 cubilin 在大鼠和人类肾小球中的合成和表达。在平行实验中,研究了 cubilin 在培养的足细胞中的表达。
这项研究根据类似于 megalin 报道的模式在大鼠和人类肾小球中鉴定出 cubilin。Cubilin 在足细胞中显示出表面表达,但也有细胞内表达。
我们的发现表明,足细胞显示了两种内吞受体,这些受体负责近端肾小管细胞中唯一有记录的蛋白质重吸收过程。