VASCULAR REMODELING BY TARGETED DISRUPTION OF TGF-β SIGNAL.
| Project/Area Number |
14571086
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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 |
Metabolomics
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| Research Institution | CHIBA UNIVERSITY |
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Principal Investigator |
YOKOTE Koutaro CHIBA UNIVERSITY, HOSPITAL, RESEARCH ASSOCIATE, 医学部附属病院, 助手 (20312944)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | TGF-β / SMAD / ATHERSCLEROSIS / SIGNAL TRANSDUCTION / VASCULAR SMOOTH MUSCLE CELLS / DIABETIC NEPHROPATHY / GROWTH FACTORS / KNOCK-OUT MICE / 遊走 |
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| Research Abstract |
Transforming growth factor-β (TGF-β) has been implicated in the development of diabetic glomerulopathy. In order to evaluate a role of Smad3, one of the major signaling molecules downstream of TGF-β, in the pathogenesis of diabetic glomerulopathy, Smad3-null mice were made diabetic with streptozotocin injection and analyzed 4 weeks after induction of diabet es. Electron microscopy revealed that the thickness of glomerular basement membrane (GBM) in wild-type diabetic mice was significantly higher than that in non-diabetic mice, whereas no appreciable GBM thickening was found in Smad3-null diabetic mice. Urinary albumin excretion was dramatically increased in wild-type diabetic mice, whereas Smad3-null diabetic mice did not show any overt albuminuria. Northern blotting revealed that mRNA levels of fibronectin and a3 chain of type IV collagen (α3Col4 ) in renal cortex of wild-type diabetic mice were approximately twice as much as those of non-diabetic mice, whereas their mRNA levels were not increased in Smad3-null diabetic mice. Real-time polymerase chain reaction (PCR) also confirmed diabetes-induced upregulation of fibronectin and α3Col4 in glomeruli of wild-type mice. Glomerular expression of TGF-β1, as assessed by real-time PCR, was enhanced to 'a similar degree in wild-type and smad3-null diabetic mice, indicating that the observed differences between wild-type and Smad3-null mice are not attributable to difference in the expression of TGF-β1. These data clearly demonstrate a critical role of Smad3 in the early phase of diabetic glomerulopathy. This may be due at least partly to the present findings that diabetes-induced upregulation of fibronectin and α3Col4 is dependent on Smad3 function.
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Report
(3 results)
Research Products
(25 results)
