2005 Fiscal Year Final Research Report Summary
ROLE OF KLOTHO GENE IN RENAL PROTECTION
| Project/Area Number |
16590776
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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 | Gunma University |
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Principal Investigator |
SAITO Yuichiro GUNMA UNIVERSITY, SCHOOL OF MEDICINE, ASSISTANT, 医学部, 助手 (30344922)
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| Project Period (FY) |
2004 – 2005
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| Keywords | ENDOTHELIUM / NITRIC OXIDE / OXIDATIVE STRESS / ALUBUMIN URIA / REMODELING / HYPERTENSION |
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| Research Abstract |
The expression of klotho mRNA in the kidney was significantly reduced in Dahl salt-sensitive hypertensive (Dahl-S) rats fed high salt (8% NaCl) diet as compared to those fed low salt (0.3% NaCl) diet (n=7). The klotho gene delivery once a week for 3 weeks induced klotho mRNA expression at the injection site. Hydroethidine, an oxidative fluorescent dye, was used to evaluate the levels of superoxide in situ. Intramuscular induction of the klotho gene decreased in superoxide production in the aorta, resulting in restoration of endothelial dysfunction from 43±6 % to 61±9 % of control rats (n=6, p<0.05). At the same time, systolic blood pressure was reduced from 262±11 mmHg to 234±6 mmHg (p<0.05). Furthermore, klotho gene delivery improved perivascular fibrosis from 0.031±0.002 to 0.011±0.001 mm^2 and reduced albuminuria from 2.5±0.4 to 0.31±0.14 g/day (n=8, p<0.05).
Our study indicates that intramusclar delivery of the klotho gene reduces oxidative stress and protects the vascular endothelium in Dhal-S rats. We suggest that induction of the klotho gene expression associated with the improvement of the endothelial function may be a potential novel therapeutic strategy for renal failure induced by hypertension.
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Research Products
(13 results)
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[Book] 循環器研究の動物たち2005
Author(s)
斎藤勇一郎, 倉林正彦
Total Pages
4
Publisher
老化抑制遺伝子klothoと血管内皮機能
Description
「研究成果報告書概要(和文)」より
