| Project/Area Number |
15K09277
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Kidney internal medicine
|
|---|
| Research Institution | Jikei University School of Medicine |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
川浪 大治 東京慈恵会医科大学, 医学部, 准教授 (50568889)
|
|---|
| Project Period (FY) |
2015-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
|
|---|
| Keywords | 糖尿病腎症 / 糸球体上皮細胞 / ポドサイト / Rho-kinase / ROCK2 |
|---|
| Outline of Final Research Achievements |
Diabetic kidney disease (DKD) remains leading cause of end stage renal disease and therefore a major burden on the healthcare system. Activation of ROCK pathway leads to the phosphorylation of downstream substrates, including myosin phosphatase target subunit, which has been postulated to control a variety of cellular functions such as cell proliferation, contraction, migration, and transcriptional regulation. A series of recent animal model studies have implicated ROCK signaling in cardiovascular and renal disease. In the present study, we identified ROCK2 as an important regulator of glomerular podocyte biability using cultured cells. In order to elucidate the role of ROCK in vivo, we generated podocyte-specific ROCK2 deletion mice. Gene expression and immunohistochemical studies will be performed in the mice to fully determine the significance of ROCK2 in the process of DKD.
|
| Academic Significance and Societal Importance of the Research Achievements |
ROCKは低分子量GTP結合タンパク質Rhoの標的タンパク質として同定されたセリン・スレオニンキナーゼである。これまでの国内外における研究により、ROCKは細胞収縮や増殖、遊走、遺伝子発現誘導等、細胞の重要な生理機能に関与することが示されている。また各種疾患モデル動物を用いた研究によってROCKの活性亢進が様々な病態を悪化させる原因となっていることが明らかになり、創薬のターゲットとして注目されている。本研究によってROCK2が糖尿病腎症の進展で重要な因子であると明らかになれば、今後これを標的とした有効な治療薬開発へつながる可能性がある。
|
