2005 Fiscal Year Final Research Report Summary
Pathophysiological analysis for tissue renin-angiotensin-system using Cre-loxP system
| Project/Area Number |
16590704
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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 |
Circulatory organs internal medicine
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| Research Institution | Yokohama City University (YCU) |
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Principal Investigator |
UMEMURA Satoshi YCU, School of Medicine, Professor, 医学部, 教授 (00128589)
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| Co-Investigator(Kenkyū-buntansha) |
FUKAMIZU Akiyoshi Tsukuba Univ., Graduate School of Life and Environmental Sciences, Professor, 大学院生命環境科学研究科, 教授 (60199172)
KIHARA Minoru YCU, School of Medicine, Associate Professor, 医学部, 準教授 (60177904)
TAMURA Kouichi YCU, School of Medicine, Associate Professor, 医学部, 準教授 (40285143)
HASHIMOTO Tatsuo YCU, School of Medicine, Assistant Professor, 医学部, 助手 (20363806)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Angiotensinogen / Kidney / Tissue renin-angiotensin-system / Mice |
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| Research Abstract |
Generation of loxP-franked (floxed) angiotensinogen mice.
The conditional angiotensinogen knockout construct was used to generate floxed angiotensinogen mice. Heterozygous mice were bred to generate homozygous mice.
Pathophysiological analysis of tissue renin-angiotensin-system
We examined the role of the renin-angiotensin system (RAS) in the regulation of macula densa cyclooxygenase-2 (COX-2) during altered dietary salt intake using Atg-/- mice. This study demonstrated that COX-2 activity in the macula densa can be regulated by salt intake through a mechanism independent of the RAS, and COX-2 expression is functionally linked to renal cortical N-NOS activity in Atg-/- mice (Nephron Physiol.2006).
The effects of altered dietary salt intake on renal endothelial nitric oxide synthase (eNOS) expression were determined in angiotensin type-1a receptor gene knockout (AT1a-/-) mice and Atg-/- mice. This study demonstrated that AT1a receptor-mediated inputs play critical roles in maintaining renal vascular eNOS expression and activity during changes in salt-water balance and systemic BP (J Am Soc Nephrol, 2004, Cell Tissue Res, 2006).
We examined the distribution of AT1 receptor-associated protein in nephron segments (Kidney Int,2006).
We evaluated the effect of angiotensin II on the pathogenesis of immune mediated colitis using Atg-/-. This study revealed that RAS is involved in the immune system in the colon (Gut,2005).
These results demonstrated that an antagonism of the RAS is a potential prophylactic strategy for the treatment of tissue damage.
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