The evaluation of molecular mechanism of glomerular injuries by serine proteases and its therapeutic application for CKD.
Project/Area Number |
17K09705
|
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 |
Kakizoe Yutaka 熊本大学, 大学院生命科学研究部(医), 助教 (70583037)
|
Project Period (FY) |
2017-04-01 – 2020-03-31
|
Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
Keywords | セリンプロテアーゼ / プラスミン / ポドサイト / 慢性腎臓病 / 糸球体障害 / セリンプロテアーゼ阻害薬 / CKD |
Outline of Final Research Achievements |
We have previously reported that serine proteases were involved in the pathogenesis of chronic kidney disease (CKD) and SP inhibitor (SPI) could have renoprotective effects. We conducted this study to identify serine proteases (SPs) which could be associated with glomerular injuries and to explore therapeutic effects of SP inhibition on glomerular injuries in CKD model rats. Urinary plasmin activity and glomerular plasmin ware increased in CKD model rats accompanied by massive urinary protein, glomerular sclerosis, and glomerular apoptotic cells. The administration of serine protease inhibitors mitigated those changes. Our study suggests that SP inhibition could be a new strategy for the treatment of CKD with glomerular injury/proteinuria.
|
Academic Significance and Societal Importance of the Research Achievements |
日本では成人人口のおよそ8人に1人が慢性腎臓病(CKD)患者と推定され、透析患者に至っては2016年度末に32万人を超えており、医療経済の面からも大きな社会問題である。本研究では酵素の1種であるセリンプロテアーゼ(SP)を標的としたCKD治療法の開発を目的とした。メタボリック症候群や食塩感受性高血圧モデル動物にSP阻害薬を投与すると、糸球体障害・蛋白尿が著明に軽減した。SPを標的とした治療法がCKD進行抑制に有用である可能性が示唆され、社会的にも重要な研究であると考えられた。
|
Report
(4 results)
Research Products
(19 results)
-
-
[Journal Article] Circulating angiopoietin-like protein 2 levels and mortality risk in patients receiving maintenance hemodialysis: a prospective cohort study2019
Author(s)
Morinaga J, Kakuma T, Fukami H, Hayata M, Uchimura K, Mizumoto T, Kakizoe Y, Miyoshi T, Shiraishi N, Adachi M, Izumi Y, Kuwabara T, Okadome Y, Sato M, Horiguchi H, Sugizaki T, Kadomatsu T, Miyata K, Tajiri S, Tajiri T, Tomita K, Kitamura K, Oike Y, Mukoyama M.
-
Journal Title
Nephrology Dialysis Transplantation
Volume: 印刷中
Issue: 5
Pages: 854-860
DOI
Related Report
Peer Reviewed / Open Access
-
-
[Journal Article] Insufficiency of urinary acid excretion of overweight or obese patients with chronic kidney disease and its involvement with renal tubular injury.2019
Author(s)
Eguchi K, Izumi Y, Nakayama Y, Inoue H, Marume T, Matsuo N, Hiramatsu A, Ono M, Kakizoe Y, Kuwabara T, Nonoguchi H, Mukoyama M.
-
Journal Title
Nephrology
Volume: 24
Issue: 11
Pages: 1131-1141
DOI
Related Report
Peer Reviewed
-
[Journal Article] Doxycycline attenuates cisplatin-induced acute kidney injury through pleiotropic effects2018
Author(s)
Nakagawa T, Kakizoe Y, Iwata Y, Miyasato Y, Mizumoto T, Adachi M, Izumi Y, Kuwabara T, Suenaga N, Narita Y, Jono H, Saito H, Kitamura K, Mukoyama M
-
Journal Title
Am J Physiol Renal Physiol
Volume: 315
Issue: 5
Pages: 1347-1357
DOI
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
-