Köhler M, Buchwalow I B, Alexander G, Christiansen M, Shagdarsuren E, Samoilova V, Hartmann E, Mervaala E M, Haller H
HELIOS Clinic, Franz Volhard Clinic at the Max Delbrück Center, Medical Faculty of the Charité, Humboldt University of Berlin, Germany.
Kidney Int. 2001 Dec;60(6):2263-73. doi: 10.1046/j.1523-1755.2001.00069.x.
Importins transport kinases, transcription factors, and viral proteins into the nucleus. Since the expression of several genes is increased in diabetic nephropathy, we tested the hypothesis that importin protein expression is increased in diabetic kidneys.
Immunohistochemistry and Western blotting were used in kidneys from streptozotocin-treated diabetic rats and from spontaneously diabetic Goto-Kakizaki rats. The effects of high glucose and mannose also were tested in cell culture experiments.
In normal rat kidneys, importin alpha isoforms were differentially expressed in glomerular cells and tubular segments, while importin alpha1/Rch1 was expressed only in tubules and peritubular cells. In diabetic rat kidneys from both models, the importin alpha isoform expression was markedly up-regulated. Western blotting revealed strong up-regulation of importin alpha7 and minor up-regulation of other isoforms. Exposure of various cell types to high glucose or mannose (25 mmol/L) led to increased expression of importins alpha3, alpha5/hSRP1, and alpha7 in different cultured cells, while up-regulation of other importin alpha isoforms was less consistent.
A specific importin alpha isoform up-regulation takes place in kidneys of diabetic rats. Diabetes is a stimulus for increased importin alpha7 expression. Thus, nuclear transport in diabetes may be increased in glomerular and tubular cells. The signaling pathways appear differentially regulated in glomeruli, proximal, and distal tubules. The enhanced nuclear transport may participate in increased gene expression and nephrosclerosis in diabetes.
输入蛋白可将激酶、转录因子和病毒蛋白转运至细胞核。鉴于糖尿病肾病中多个基因的表达增加，我们检验了如下假设：糖尿病肾脏中输入蛋白的表达会增加。
对经链脲佐菌素处理的糖尿病大鼠以及自发性糖尿病Goto-Kakizaki大鼠的肾脏进行免疫组织化学和蛋白质印迹分析。同时在细胞培养实验中检测高糖和甘露糖的作用。
在正常大鼠肾脏中，输入蛋白α亚型在肾小球细胞和肾小管节段中存在差异表达，而输入蛋白α1/Rch1仅在肾小管和肾小管周围细胞中表达。在两种模型的糖尿病大鼠肾脏中，输入蛋白α亚型的表达均显著上调。蛋白质印迹分析显示输入蛋白α7有强烈上调，其他亚型有轻微上调。将各种细胞类型暴露于高糖或甘露糖（25 mmol/L）中，可导致不同培养细胞中输入蛋白α3、α5/hSRP1和α7的表达增加，而其他输入蛋白α亚型的上调则不太一致。
糖尿病大鼠肾脏中发生了特定输入蛋白α亚型的上调。糖尿病是输入蛋白α7表达增加的刺激因素。因此，糖尿病时肾小球和肾小管细胞中的核转运可能增加。肾小球、近端和远端肾小管中的信号通路似乎受到不同的调节。增强的核转运可能参与了糖尿病时基因表达增加和肾硬化的过程。
