2014 Fiscal Year Final Research Report
Pathological significance of Nox isoforms of NADPH oxidase in diabetic nephropathy
| Project/Area Number |
25860694
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Kidney internal medicine
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
COOPER Mark Baker IDI Heart and Diabetes Institute, Prof.
CHANNON Keith Oxford University, Prof.
TANNER George Indiana University, Prof.
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| Research Collaborator |
KASHIHARA Naoki 川崎医科大学, 医学部, 教授 (10233701)
SATOH Minoru 川崎医科大学, 医学部, 准教授 (70449891)
KUWABARA Atsunori 川崎医科大学, 医学部, 講師 (50368627)
YORIMITSU Daisuke 川崎医科大学, 医学部, 臨床助教 (50412177)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Keywords | 糖尿病性腎症 / NADPHオキシダーゼ / Nox |
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| Outline of Final Research Achievements |
Activated NADPH oxidase is associated with progression of diabetic nephropathy, but the pathological significance of Nox isoforms, cell membrane components of NADPH oxidase, remains to be elucidated. Here, we investigated ameliorative effects of genetic manipulation of Nox1 and Nox4, on diabetic mice kidneys, to clarify the role of Nox isoforms in diabetic nephropathy. Diabetic/control knockout (KO)/wild-type mice were used for the examination at ～20 weeks after induction of diabetes. Diabetes-induced albuminuria was attenuated in both Nox1KO and Nox4KO mice, while the glomerular sclerosis was mitigated in only Nox1KO kidneys. Increased mRNA expressions of Nox2, fibronectin, and alpha-SMA in diabetic kidneys were suppressed in only Nox1KO mice. Accumulation of nitrotyrosine in glomeruli of diabetic kidneys was completely suppressed in Nox1KO mice, although it was reduced insufficiently in Nox4KO mice. Collectively, activated Nox1 may contribute to progression of diabetic nephropathy.
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| Free Research Field |
腎臓学
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