| Project/Area Number |
09671180
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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 | Jikei University School of Medicine |
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Principal Investigator |
KAWAMURA Tetsuya Jikei University School of Medicine Department of Medicine II,Lecturer, 内科学講座・第2, 講師 (20161367)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAZAKI Yoichi Jikei University School of Medicine Department of Medicine II,Instructor, 内科学講座・第2, 助手 (60266690)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1997: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | glomerular endothelial cell / static stretch / mecharical strain / nitric oxide / endothelial NOS / vascular endothelial cell / cyclic GMP / brady kinin / MCP-1 / 糸球体硬化 / マクロファージ / メサンギウム細胞 / 細胞外基質 / ICAM-1 / M-CSF |
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| Research Abstract |
In the present study, we examined the effect of static stretch to glomerular endothelial cells (GEC) and vascular endothelial cells (VEC) on the expression of nitric oxide synthase (NOS) and the production of nitric oxide (NO) by these cells upon the stimulation by bradykinin.
Northern blot analysis and RT-PCR revealed that mRNA levels for endothelial NOS (eNOS) were not significantly different between the cells with and without exposure to 30-40 % static stretch for up to 48hr. In contrast, it was clearly demonstrated by Western blot analysis that the expression of eNOS protein was down-regulated in VEC exposed to static stretch for 24 hours in a stretch-degree dependent manner. Moreover, 10^<-6> M bradykinin markedly increased cGMP contents in untreated VEC, whereas this effect was completely abolished when VEC were exposed to 30% stretch for 24 hours prior to the stimulation by bradykinin. These results indicate that the expression of eNOS protein may be down-regulated in VEC when they are exposed to a high degree of mechanical stretch, leading to a compromised production of NO in response to eNOS agonists. We are in the process of examining the effect of static stretch to GEC on the production of NO upon the stimulation by bradykinin, in order to elucidate a role of a high degree of mechanical stretch to GEC in the regulation of glomerular microcirculation.
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