2005 Fiscal Year Final Research Report Summary
Investigation of the pathophysiological significance of big mitogen-activated protein kinase 1 in diabetic microangiopathy for the development of molecular-targeted drugs
| Project/Area Number |
16590195
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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 |
General pharmacology
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| Research Institution | Nara Medical University (2005)
The University of Tokushima (2004) |
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Principal Investigator |
YOSHIZUMI Masanori Nara Medical University, Pharmacology, Professor, 医学部, 教授 (60294667)
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| Co-Investigator(Kenkyū-buntansha) |
TAMAKI Toshiaki Univ. Tokushima, Inst. Health Biosciences, Professor, 大学院・ヘルスバイオサイエンス研究部, 教授 (80179879)
TSUCHIYA Koichiro Univ. Tokushima, Inst. Health Biosciences, Assoc. Professor, 大学院・ヘルスバイオサイエンス研究部, 助教授 (70301314)
KAGAMI Shoji Univ. of Tokushima, Inst. Health Biosciences, Professor, 大学院・ヘルスバイオサイエンス研究部, 教授 (00224337)
KANEMATSU Yasuhisa Univ. of Tokushima, Inst. Health Biosciences, Assist. Professor, 大学院・ヘルスバイオサイエンス研究部, 助手 (90363142)
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| Project Period (FY) |
2004 – 2005
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| Keywords | MAP kinases / Big MAP kinase 1 / Diabetic microangiopathy / OLETF rat / Cuff-injury / Platelet derived growth factor / SHP-2 / Gab1 |
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| Research Abstract |
In the current research project, we investigated the pathophysiological significance of big mitogen-activated protein kinase 1 in diabetic microangiopathy for the development of molecular-targeted drugs.
1)In the type 2 diabetic rat model OLETF, BMK1 was activated in the small artery at 30 weeks of age without apparent complications with diabetes mellitus. From these findings, it was suggested that BMK1 activation is involved in the pathogenesis of diabetic microangiopathy.
2)In the mouse model of inflammatory vascular disease, big mitogen-activated protein kinase 1 (BMK1) was activated at the site of adventitia of cuff-injured femoral artery. At the site of cuff-injured artery, neointimal formation and infiltration of mononuclear cells were observed. These findings suggest that BMK1 is involved in the pathogenesis of inflammatory vascular remodeling.
3)In experiments using cultured rat aortic smooth muscle cells (RASMC), aldosterone stimulated BMK1 activation. BMK1 activation by aldosterone was inhibited by treatment with eplerenone, a mineralocorticoid receptor blocker. Aldosterone-induced RASMC proliferation was inhibited by genetic BMK1 inhibition.
4)In RASMC PDGF stimulated BMK1 activation in a time and concentration-dependent manner. PDGF also stimulated RASMC migration, which was inhibited by a transfection with dominant-negative MEK5.
From these in vivo and in vitro findings, BMK1 is suggested to be involved in diabetic microangiopathy and BMK1 may be one of the drug targets for treatment of complications with diabetes mellitus.
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Research Products
(19 results)
