| Project/Area Number |
16K09637
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Kidney internal medicine
|
|---|
| Research Institution | Kurume University |
|---|
Principal Investigator |
FUKAMI KEI 久留米大学, 医学部, 教授 (80309781)
|
|---|
| Project Period (FY) |
2016-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Keywords | AGEs / RAGE / AGEs-RAGE / 高血圧症 / aptamer / 糖尿病 / SGLT2 / Diabetic Nephropathy / 脳腎連関 / アプタマー / 母体環境 / メタボリック症候群 / 腎臓病 |
|---|
| Outline of Final Research Achievements |
Advanced glycation endproducts (AGEs) stimulate intracellular pathways through the receptor for AGEs (RAGE), which is thought to be involved in the brain-kidney injury. Uninephrectomized 8-week-old C57Bl/6J male mice were divided into three groups; 4% salt diet (control), 4% salt diet with DOCA (50mg), and DOCA with hydralazine (Hyd).Administration of DOCA significantly increased UAE independent of blood pressure. Renal RAGE protein expression and plasma carboxymethyl lysine (CML) levels were elevated in DOCA-induced HN mice. RAGE was co-localized with MR in podocytes by immunohistochemical analysis. DOCA-induced increase in UAE, renal ROS generation, RAGE expression, plasma CML levels, GTP-bound Rac1 activation, and MR overexpression were significantly inhibited by the administration of RAGE-aptamer. AGEs-RAGE axis and Rac1-MR pathway may be correlated with each other, which could lead to kidney injury in HN. Next we investigate the role of AGEs-RAGE system on brain-kidney injury.
|
| Academic Significance and Societal Importance of the Research Achievements |
わが国の現状の問題点として、慢性腎臓病患者の増大、とりわけ透析患者数の増大と、脳卒中罹患の増加がある。脳と腎臓はお互いに連携を取り合っている可能性が示唆されており、今回はAGEs-RAGE系に着目して研究を行った。AGEs-RAGE系の活性化に今回脳傷害にも重要な因子であるMRが関与していることが明らかとなり、AGEs-RAGE-MR系の遮断のために我々はRAGEノックアウトマウス、RAGE-aptamerを使用して検討を行った結果、RAGEを遮断することで腎傷害が著明に改善することを突き止めた。今後は創薬を念頭に脳傷害に対するRAGE-aptamerの効果を検討していく予定である。
|
