2000 Fiscal Year Final Research Report Summary
The moleular biological investigation of the role of PAF in the progressive renal disease
| Project/Area Number |
11671029
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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 | University of Tokyo |
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Principal Investigator |
NAKAO Akihide University of Tokyo Department of Nephrology and Endocrinology, lecturer assistant prof., 医学部・附属病院, 講師 (10159056)
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| Co-Investigator(Kenkyū-buntansha) |
NOIRI Eise University of Tokyo Department of Nephrology and Endocrinology, lecturer assistant prof., 医学部・附属病院, 助手 (00301820)
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| Project Period (FY) |
1999 – 2000
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| Keywords | progressive renal disease / cellular infiltration / chemotaxis / LTB_4 / LTA4 hydrolase / ischemic reperfusion injury |
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| Research Abstract |
Leukotriene B4 (LTB4), like PAF, is a kind of lipid mediator whose actions include the degranulations of polymorphonuclear leukocytes, the chemotaxis of valuable cells, and the adhesions of neutrophiles to vascular endothelial cells. Their biological effects are mediated through its specific receptor. Since the progression of renal disease has been reported to be reduced by the maneuvers such as inhibitions of infiltration of macrophage or neutrophiles, we investigated the role of LTB4 in the renal disease.
Firstly, we examined the distribution of leukotriene A4 hydrolase which catalyze the final step of the synthesis of LTB4, using RT-PCR, western blotting, and immunohistochemistry. The enzyme was shown to be localized ubiquitously in the kidney by the methods mentioned above. Indeed, glomeruli as well as tubules could synthesize LTB4 under the stimulation of arachidonic acid and calcium ionophore (Kidney Int 1999). It was also confirmed that the expression of this enzyme was also upregulated by the increase of the pressure stimulation by angiotensin II in the view of northern blotting, western blotting, and the enzyme activities (FEBS lett). Following the cloning of human LTB4 receptor, we cloned rat LTB4 receptor (Biochem Biophys Res Commun 1999). Finally, we investigated the role of LTB4 in the reperfusion injury of rat kidneys, a model of acute renal failure. It was shown that LTB4 receptor engineered CHO cells migrated into tubular and interstitial cells, and that the treatment with the LTB4 receptor antagonist mitigated the infiltration of inflammatory cells and ameliorated renal functions. These results suggested the important role of LTB4 in the reperfusion injury (Proc Natl Acad Sci USA 2000).
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[Publications] Nakao A, Watanabe T, Ohishi N, Toda A, Asano K, Taniguchi S, Nosaka K, Noiri E, Suzuki T, Sakai T, Kurokawa K, Shimizu T, Kimura S.: "Ubiquitous localization of leukotriene A4 hydrolase in the rat nephron."Kidney Int.. 55(1). 100-8 (1999)
Description
「研究成果報告書概要(欧文)」より
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