The role of Ubiquitin-Proteasome system in the kidney injury and regeneration
| Project/Area Number |
15K15329
|
|---|
| Research Category |
Grant-in-Aid for Challenging Exploratory Research
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Kidney internal medicine
|
|---|
| Research Institution | Kyoto University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Renkei-kenkyūsha) |
KANAI Yoshikatsu 大阪大学, 医学(系)研究科(研究院), 教授 (60204533)
|
|---|
| Project Period (FY) |
2015-04-01 – 2017-03-31
|
| Project Status |
Completed (Fiscal Year 2016)
|
| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Keywords | ユビキチンプロテアソーム系 / 腎臓病 / ユビキチン / プロテアソーム / 腎臓 / 尿細管 / 線維芽細胞 / 蛋白質 / 遺伝子 |
|---|
| Outline of Final Research Achievements |
The aim of this study was to elucidate the role of the ubiquitin-proteasome system (hereafter referred to as the UPS system) in the maintenance of kidney homeostasis. We generated conditional knockout mice lacking a certain proteasome component in a proximal tubule-specific manner by injecting tamoxifen into offsprings between our previously generated proximal tubule-specific inducible Cre mice and floxed mice of the proteasome component. We found that the abovementioned conditional knockout mice died from renal failure. The knockout mice showed the signs of tubular damages and impaired autophagic flux.
|
| Academic Significance and Societal Importance of the Research Achievements |
腎臓においては古くから腎臓の恒常性維持に重要な役割を果たすタンパクがUPSで分解されることが知られていたが、UPSが総体として腎臓の恒常性維持、生理機能をどのように制御しているかは明らかではなかった。高等生物では数百種類に及ぶユビキチンリガーゼがあることもその総合的な機能解析を困難にしていた。本系は、UPS系が近位尿細管の恒常性維持に果たす役割を示す点で重要である。UPS系阻害薬は臨床でも使用されており、その観点からも本解析は意義がある。
|
Report
(3 results)
Research Products
(14 results)
-
[Journal Article] Time-dependent dysregulation of autophagy in the kidney: implications in aging and mitochondrial homeostasis2016
Author(s)
Takeshi Yamamoto, Yoshitsugu Takabatake, Tomonori Kimura, Atsushi Takahashi, Tomoko Namba, Jun Matsuda, Jun-ya Kaimori, Isao Matsui, Harumi Kitamura, Taiji Matsusaka, Fumio Niimura, Motoko Yanagita, Yoshitaka Isaka, Hiromi Rakugi
-
Journal Title
Autophagy
Volume: in press
Related Report
Peer Reviewed
-
[Journal Article] Severity and frequency of proximal tubule injury determines renal prognosis2015
Author(s)
Koji Takaori, Jin Nakamura, Shinya Yamamoto, Hirosuke Nakata, Yuki Sato, Masayuki Takase, Masaaki Nameta, Tadashi Yamamoto, Aris N. Economides, Kenji Kohno, Hironori Haga, Kumar Sharma, Motoko Yanagita
-
Journal Title
J Am Soc Nephrol
Volume: in press
Related Report
Peer Reviewed / Int'l Joint Research
-
-
[Journal Article] MicroRNA-26a inhibits TGF-β-induced extracellular matrix expression in podocytes by targeting CTGF and is downregulated in diabetic nephropathy.2015
Author(s)
Koga K, Yokoi H, Mori K, Kasahara K, Kuwabara T, Imamaki H, Ishii A, Mori KP, Kato Y, Ohno S, Toda N, Saleem MA, Sugawara A, Nakao K, Yanagita M, Mukoyama M.
-
Journal Title
Diabetologia
Volume: 58
Issue: 9
Pages: 2169-80
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
-
[Journal Article] Exploring the origin and limitations of kidney regeneration.2015
Author(s)
Endo T, Nakamura J, Sato Y, Asada M, Yamada R, Takase M, Takaori K, Oguchi A, Iguchi T, Higashi AY, Ohbayashi T, Nakamura T, Muso E, Kimura T, Yanagita M.
-
Journal Title
J Pathol.
Volume: 236(2)
Issue: 2
Pages: 251-63
DOI
Related Report
Peer Reviewed
-
-
-
-
[Presentation] 肥満と腎障害2015
Author(s)
柳田素子
Organizer
第36回日本肥満学会
Place of Presentation
名古屋国際会議場
Year and Date
2015-10-02
Related Report
Invited
-
-
-
-
-
