| 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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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | ENDOTHELIUM / NITRIC OXIDE / OXIDATIVE STRESS / ALUBUMIN URIA / REMODELING / HYPERTENSION / 加齢 / 高血圧 / アルブミン排泄 / 腎不全 |
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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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