The study for pathogenesis of diabetic nephropathy
| Project/Area Number |
16590801
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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 | Tokai University |
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Principal Investigator |
SUZUKI Daisuke Tokai University, School of Medicine, Associate Professor, 医学部, 助教授 (80276815)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Diabetic nephropathy / In situ hybridization / Type IV collagen / Type VI collagen / MMP / TIMP / cytokine / Growth factor / In situ hybridization / In situ hydridization |
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| Research Abstract |
The pathological change in mesangial expansion on diabetic nephropathy (DN) is characterized by an increase in all intrinsic components of mesangial matrix, such as extracellular matrix (ECM) proteins including type IV (IV-C), V and VI collagens and fibronectin (FN). On the other hand, matrix metalloproteinase-2,3,9 (MMP-2,3,9) degrade ECM proteins and tissue inhibitors of metalloproteinase-1 and 2 (TIMP-1 and 2) are known to inhibit the activity of MMPs. Although the balance between ECM production and degradation is important, these relationships are not fully understood in DN. Therefore, we examined the balance between ECM production and degradation and its role in the pathogenesis of DN using in situ hybridization (ISH) and immunohistochemical staining.
First, we measured the total glomerular area and glomerular areas of ECM protein antibody positive staining using an automatic image analyzer. Then, we calculated the percentage of positively stained areas. Second, we examined the expression of mRNAs of ECM protein and MMPs and TIMPs using in situ hybridization. The expression level of these mRNAs was quantitated as a percentage of total cells. The relationship among the degree of glomerular mesangial expansion, the percentage of anti-ECM protein antibody positively stained areas and the expression of these mRNAs was investigated.
Both of the percentage of ECM protein positive areas and the cells positive for ECM protein mRNA were significantly higher in DN than in normal control samples (controls). These were significantly correlated with the degree of mesangial expansion in DN. On the other hand, the percentage of cells positive for MMPs and TIMPs mRNA was significantly higher in controls than in DN. Furthermore, the percentage of cells positive for MMPs and TIMPs mRNA was inversely correlated with mesangial expansion and the percentage of ECM protein positive areas in DN.
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Report
(3 results)
Research Products
(20 results)
