Increased importin alpha protein expression in diabetic nephropathy

Background. Importins transport kinases, transcription factors, and viral p roteins into the nucleus. Since the expression of several genes is increase d in diabetic nephropathy, we tested the hypothesis that importin protein e xpression is increased in diabetic kidneys. Methods. Immunohistochemistry and Western blotting were used in kidneys fro m 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. Results. In normal rat kidneys, importin a isoforms were differentially exp ressed in glomerular cells and tubular segments, while importin alpha1/Rch1 was expressed only in tubules and peritubular cells. In diabetic rat kidne ys from both models, the importin a isoform expression was markedly up-regu lated. Western blotting revealed strong up-regulation of importin alpha7 an d minor up-regulation of other isoforms. Exposure of various cell types to high glucose or mannose (25 mmol/L) led to increased expression of importin s alpha3, alpha5/hSRP1, and alpha7 in different cultured cells, while up-re gulation of other importin a isoforms was less consistent. Conclusions. A specific importin a isoform up-regulation takes place in kid neys of diabetic rats. Diabetes is a stimulus for increased importin alpha7 expression. Thus, nuclear transport in diabetes may be increased in glomer ular and tubular cells. The signaling pathways appear differentially regula ted in glomeruli, proximal, and distal tubules. The enhanced nuclear transp ort may participate in increased gene expression and nephrosclerosis in dia betes.