Different Distribution And Expression Of Glycogen Synthase Kinase-3α And β In Kidney Of Diabetic Nephropathy Mice

Purposes:To investigate the different distribution and expression of glycogen synthase kinase-3(GSK3) α and β in kidney of diabetic nephropathy mice as well as their potential role in the diabetic nephropathy (DN).Methord:C57BL/6mice were randomly divided into control group (CON) and experimental group (DN), DN models were induced by i.p. injected with streptozotocin., normal mice were provided as controls. Two weeks later, collect the mice blood, random urine and renal tissues of each group. Use the method of picric acid to determine the blood and urine creatinine, the protein was measured by the BCA kit. The localization of GSK3was determined by confocal immunofluorescence laser scanning, and the expression of GSK3and phospho-GSK3in the cortex, outer medullary and inner medullary of kidney in each group was detected by western blotting, as well as the cortex expression of β-catenin and podocin.Results:(1) Blood glucose and the ratio of urine protein/creatinine of DN group mice were obviously higher than that of CON group mice, the expression of podocin was decreased in the cortex of DN mice as compared to that of CON mice. The blood protein and serum creatinine of two groups didn’t have significant difference.(2) GSK3β was widely expressed in glomerular mesangial, podocyte, proximal tubules, cortical and medullary thick ascending limbs and collecting ducts, while GSK3a was only expressed in inner medulla collecting ducts of DN and CON mice. Meanwhile, GSK3α and β were translocated to the luminal membrane of the epithelial cells in the inner medulla collecting ducts.(3) In DN mice, the expression of p-GSK3β in the cortex, GSK3α and P-GSK3α in the inner mudulla were significantly higher than those of CON mice.(4) Compared with the CON group, the expression of β-catenin in DN mice cortex was significantly decreased.Conclusion:GSK3α and β present a different distribution phenotype in mouse kidney, the distribution and activity of GSK3α and β in DN mice were changed in DN mice. Combing with the decreasing expression of GSK3targeted protein β-catenin in DN kidney, our study indicates that GSK3α and β may involve in the development of DN by affecting the expression of β-catenin.