Department of Infection Immunity and Inflammation, University of Leicester, Leicester, UK.
Department of Nephrology, Leicester General Hospital, Leicester, UK.
Nephrol Dial Transplant. 2018 Jun 1;33(6):934-943. doi: 10.1093/ndt/gfx321.
Filtered proteins, including albumin, are reabsorbed in the proximal tubule (PT) mediated by megalin, cubilin and the neonatal Fc receptor (FcRn). Proteinuria is an important renal biomarker linked to poor prognosis but expression of these key receptors is not well studied.
Megalin expression was determined at protein and messenger RNA (mRNA) levels in kidneys from proteinuric patients, and the expression of megalin, cubilin and FcRn was examined in the kidneys of mice with protein-overload proteinuria. The presence of receptors in the urine of proteinuric and control mice was also studied.
In nephrotic patients, megalin expression is reduced while mRNA is increased. In proteinuric mice megalin, cubilin and the neonatal FcRn protein are all reduced in PTs. Megalin and FcRn mRNA are increased in proteinuric mice, whereas that for cubilin was reduced. In proteinuric mice increased urinary excretion of each of these endocytic receptors was observed.
It is concluded that in proteinuria, expression of all the key protein re-absorptive receptors is significantly reduced in the PT in association with increased turnover and urinary shedding.
包括白蛋白在内的过滤蛋白通过巨球蛋白、巨球蛋白和新生 Fc 受体（FcRn）在近端小管（PT）中被重吸收。蛋白尿是与预后不良相关的重要肾脏生物标志物，但这些关键受体的表达尚未得到充分研究。
在蛋白尿患者的肾脏中，从蛋白质和信使 RNA（mRNA）水平确定巨球蛋白的表达，并在蛋白过载性蛋白尿小鼠的肾脏中检查巨球蛋白、巨球蛋白和 FcRn 的表达。还研究了蛋白尿和对照小鼠尿液中受体的存在。
在肾病患者中，巨球蛋白的表达减少，而 mRNA 增加。在蛋白尿小鼠中，PT 中的巨球蛋白、巨球蛋白和新生 FcRn 蛋白均减少。蛋白尿小鼠中巨球蛋白和 FcRn mRNA 增加，而巨球蛋白 mRNA 减少。在蛋白尿小鼠中，观察到每种内吞受体的尿液排泄均增加。
因此，在蛋白尿中，PT 中所有关键蛋白重吸收受体的表达均显著降低，与周转率增加和尿液流失有关。
