2005 Fiscal Year Final Research Report Summary
The role of GSK-3 dependent transcriptional factor on glomerulo injury
| Project/Area Number |
16590791
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Kumamoto University |
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Principal Investigator |
INOUE Takeaki Kumamoto University, University Hospital, associate professor, 医学部附属病院, 講師 (90322312)
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| Co-Investigator(Kenkyū-buntansha) |
TOMITA Kimio Kumamoto University, Graduate School of Medical Sciences, professor, 大学院・医学薬学研究部, 教授 (40114772)
NONOGUCHI Hiroshi Kumamoto University, Graduate School of Medical Sciences, assistant professor, 大学院・医学薬学研究部, 助教授 (30218341)
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| Project Period (FY) |
2004 – 2005
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| Keywords | glycogen synthase kinase β / podocyte / tubules / streptozocin / diabetic rat / 糖尿病ラット |
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| Research Abstract |
Diabetes mellitus is one of main causes of ESRD in many countries. Insulin inhibits glycogen synthase kinase β (GSK3β) via the phosphorylation of ser-9, and Contributes to the stimulation of glycogen and protein synthase. Blunted regulation of GSK3β is linked to several pathological conditions, such as diabetes and Alzheimer's disease. However, the pathophysiological role of GSK3β in diabetic nephropathy is still unknown. In this study, distribution of GSK3β mRNA along the nephron of rat was investigated using microdissection and reverse transcription coupled real time PCR method. GSK3β mRNA expressed in all nephron segments. The mRNA was abundant in glomerulus and distal tubules. In proximal tubules, relative small amount of GSK3β mRNA was observed. Diabetic rat was prepared by streptozocin injection (60mg/kg) through the tail vein. 1 week after the injection, blood sugar was significantly increased in rats with streptozocin injection (415±37 mg/dl) compared with control rats (112±25m
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g/dl). Real time PCR showed that the GSK3β mRNA expression was increased by 82±17% in glomerulus and by 40±11% in proximal tubules in diabetic rat. In contrast, GSK3β mRNA did not change in distal tubules. Western blot analysis using the monoclonal antibody specific to rat GSK3β and P-ser9-GSK3β, phosphorylated inactive form of GSK3β was performed. Western blot analysis revealed that GSK3β was significantly increased by 50±8% in glomerulus of diabetic rat compared with control rat. This increase was sustained at least up to 3 weeks. On the other hand, P-ser-GSK3β protein did not change in diabetic rat. Immunohistochemical analysis was performed using anti-GSK3β monoclonal antibody. GSK3β expression was evident at the peripheral area of the capillary. Some of them was colocalized with podocin, a marker protein for podocyte. Majority of synaptopodin, another marker for podocyte, was colocalized with GSK3β, indicated the expression of GSK-3β in podocyte
Expression of GSK3β along the nephron was demonstrated and augmentations of GSK3β mRNA and active form of GSK3β protein has become evident in the glomerulus of diabetic rat. These data suggested that early increase of GSK3β expression in the glomeruli could play an important role for the pathogenesis of diabetic nephropathy. Less
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Research Products
(8 results)
