Project/Area Number |
26461226
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Kidney internal medicine
|
Research Institution | Kumamoto University |
Principal Investigator |
MUKOYAMA Masashi 熊本大学, 大学院生命科学研究部(医), 教授 (40270558)
|
Co-Investigator(Renkei-kenkyūsha) |
MORI Kiyoshi 静岡県立大学, 薬学部, 特任教授 (60343232)
|
Research Collaborator |
KUWABARA Takashige 熊本大学, 大学院生命科学研究部, 助教 (00393356)
|
Project Period (FY) |
2014-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | 腎臓学 / 内分泌学 / メタボリック症候群 / 糖尿病性腎症 / レニン・アンジオテンシン系 / ナトリウム利尿ペプチド / N型カルシウムチャネル / 自然炎症 / 高血圧 / アルドステロン / マクロファージ / metabolic syndrome / 肥満症 / renin-angiotensin system |
Outline of Final Research Achievements |
Lifestyle-related noncommunicable diseases such as diabetes, obesity and hypertension are the major risk for metabolic kidney diseases, in which endocrine dysregulation in organ-organ or cell-cell communications in the kidney may be suggested. We investigated roles of humoral factors in this pathophysiology. We found that the natriuretic peptide (ANP and BNP) receptor GC-A in podocytes is important in protecting against aldosterone-induced glomerular injury in mice. We also found the role of N-type calcium channels in sympathetic nerve activation and podocyte injury in obese diabetic mice with nephropathy. Finally, we found the pathogenic role of local homeostatic inflammation driven by toll-like receptor 4 and its endogenous ligand myeloid-related protein 8 (MRP8), a macrophage-derived proinflammatory factor, in mouse models of diabetes-hyperlipidemia as well as proliferative nephritis. These findings may provide potential therapeutic strategies for metabolic kidney diseases.
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