| Project/Area Number |
23591209
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Kidney internal medicine
|
|---|
| Research Institution | Kawasaki Medical School |
|---|
Principal Investigator |
KOMAI Norio 川崎医科大学, 医学部, 准教授 (40368626)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
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, 講師 (70449891)
|
|---|
| Project Period (FY) |
2011 – 2013
|
| Project Status |
Completed (Fiscal Year 2013)
|
| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
|
|---|
| Keywords | アルブミン尿 / 内皮障害 / 一酸化窒素 / 慢性腎臓病 / 酸化ストレス / 活性酸素種 / 内皮細胞 / 糸球体 / 血管透過性 |
|---|
| Research Abstract |
Albuminuria is an independent risk marker for development of cardiovascular disease. We hypothesized that albuminuria could be caused by glomerular endothelial injuries/dysfunctions. We have successfully developed the novel in vivo-imaging technique by which we can visualize microcirculation and filtration status by using 2-phton lasermicroscopy. We found that in diabetes, endothelial nitric oxide synthase (eNOS) produces superoxide anion rather than nitric oxide, referred to as "eNOS uncoupling," which contributes to endothelial dysfunction, albuminuria, and diabetic nephropathy. Reduced levels of endothelium-derived tetrahydrobiopterin (BH4), an essential cofactor for eNOS, promote eNOS uncoupling. We also demonstrated that renin-angiotensin system is deeply associated with generation of oxidative stress through activation of NADPH-oxidase. We have elucidated that maintenance of endothelial integrity ameliorates diabetic nephropathy.
|
