Project/Area Number |
23790951
|
Research Category |
Grant-in-Aid for Young Scientists (B)
|
Allocation Type | Multi-year Fund |
Research Field |
Kidney internal medicine
|
Research Institution | Iwate Medical University |
Principal Investigator |
YONEZAWA Sei 岩手医科大学, 薬学部, 助教 (50469988)
|
Project Period (FY) |
2011 – 2012
|
Project Status |
Completed (Fiscal Year 2012)
|
Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | ネフローゼ / 脂質 / リポソーム / 慢性腎疾患 |
Research Abstract |
In this study, we focus on lipids accumulating in the renal tubular epithelial cells of chronic kidney disease. But the reason why lipids accumulate in the kidney is unknown. So we looked into the mechanism and purpose of lipid accumul ation. Moreover, we tried to establish foundations for clinical application which targeted lipids for treatment of kidney disease.At first, we have investigated the mechanisms of lipid accumulation by using renal tubular epithelial cells. Hypoxia induci ble factor-1 alpha and ATP-binding cassette protein A1 played an important role in the control of intracellular lipids in cells of the kidneys. Moreover, we found out the fact that intracellular lipids could increase by the addition of inflammatory stimulu s. The increase of intracellular lipids described above could be inhibited by overexpression of liver X receptor alpha. This result suggests importance of the changes of lipid control in the kidney. Then, we tried to establish of selective drug delivery system toward kidney. After i.v. injection, liposomes which consist of cholesterol and cationic phospholipid had little occasion to get to kidney. On the other hand, anionic liposomes which was hydrophilic could accumulated in the kidney of the chronic kidney disease model.We demonstrated importance of lipid control in kidney and a part of its mechanisms. A detailed consideration about mechanisms of intracellular lipids and progress of drug delivery system could lead to a novel treatment of kidney disease.
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