| Project/Area Number |
11470218
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | OKAYAMA UNIVERSITY |
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Principal Investigator |
MAKINO Hirofumi Okayama University, Graduate School of Medicine and Dentistry, Professor, 大学院・医歯学総合研究科, 教授 (50165685)
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| Co-Investigator(Kenkyū-buntansha) |
HIDA Kazuyuki Okayama University, Hospital, Senior Residentd, 医学部・附属病院, 医員
SHIKATA Tenichi Okayama University, Hospital, Lecturer, 医学部・附属病院, 講師 (00243452)
WADA Jun Okayama University, Graduate School of Medicine and Dentistry, Assistant, 大学院・医歯学総合研究科, 助手 (30294408)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥16,500,000 (Direct Cost: ¥16,500,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥13,700,000 (Direct Cost: ¥13,700,000)
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| Keywords | diabetic nephropathy / glomerular hyperfiltration / DNA array / CD-1 mouse / molecular cloning / gene expression profiling / glomerulosclerosis |
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| Research Abstract |
Background. To elucidate molecular mechanism of diabetic nephropathy, high density DNA filter array was employed for the survey of gene expression profile of streptozotocin-induced diabetic CD-1 (ICR) mice kidney.
Methods. Ten-week-old CD-1 male mice were divided into four groups (1) control, (2) unilaterally nephretomized (UX) mice, (3) STZ-induced diabetic (STZ) mice, and (4) STZ mice with unilateral renal ablation (STZ-UX). The pathological changes were examined at 24 weeks after the induction. The gene expression profile was compared between the control and STZ mice by Gene Discovery Array (GDA).
Results. The glomeruli in UX mouse kidney showed prominent glomerular hypertrophy, while the accumulation of mesangial matrix was minimal. Both STZ and STZ + UX mice had significant glomerular hypertrophy and glomerulosclerosis and lesions were not enhanced by renal ablation. By comparison between control and STZ mice, 16 clones that increased in expression with the induction of diabetes and 65 clones that decreased in diabetic kidneys were identified. The 37 known genes were related to glucose and lipid metabolism, ion transport, transcription factors, signaling molecules and extracellular matrix-related molecules. The genes known to be involved in cell differentiation and organogenesis in various tissues, i.e. Unc-18 homologue, POU domain transcription factor 2, lunatic fringe gene homolog, fibrous sheath component 1, Sox-17, fibulin 2, and MRJ, were found to be differentially expressed in early phase of diabetic kidneys.
Conclusions. Hyperglycemia was major determinant of glomerulosclerosis in STZ-induced diabetic CD-1 mice and the altered gene expression in the early phase of diabetic kidney may be critical for the development of diabetic nephropathy.
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