| Project/Area Number |
08671290
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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 | Kumamoto University |
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Principal Investigator |
KIYAMA Shigeru Kumamoto University School of Medicine Assistant professor, 医学部, 助手 (80274710)
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| Co-Investigator(Kenkyū-buntansha) |
TOMITA Kimio Kumamoto University School of Medicine Professor, 医学部, 教授 (40114772)
NONOGUCHI Hiroshi Kumamoto University School of Medicine Associate professor, 医学部・附属病院, 講師 (30218341)
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| Project Period (FY) |
1996 – 1997
|
| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1997: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
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| Keywords | acute renal failure / endothelin / gene / glomerulus / tubule |
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| Research Abstract |
Endothelin-1 (ET-1) is believed to play a significant role in acute renal failure (ARF) induced by cyclosporin A (CYA). Recently, the cDNA sequence encoding endothelin converting enzyme-1 (ECE-1), which produces the active form of ET-1 from big ET-1, has been reported. To elicit a role for ECE-1 in the glomerulus and tubular dysfunction induced by CYA,we studied the effect of CYA on ECE-1 mRNA and protein expression in rat kidney, and on prepro ET-1 (ppET-1), endothelin A nad B type receptor (ETAR and ETBR) mRNA expression in glomeruli. ECE-1mRNA was detected in glomeruli and in whole nephron segments. ECE-1 mRNA expression was down regulated in all nephron segments at 24 hr after CYA injection. Protein levels were also down regulated in glomeruli and in the outer and inner medulla. CYA caused a rapid increase of ppET-1 mRNA in glomeruli at 30-60 min after injection, which was followed by an increase of the plasma ET-1 level. These increase were followed by decreased expression of ECE-1, ETAR and ETBR at 6 hr after injection, while the serum creatinine level increased at 24 hr after the injection. it is suggested that down regulation of glomerular and tubular ECE-1 expression accurs to minimize the effects of ET-1 in CYA-induced ARF.
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