The investigation of functional role of CCR4-NOT compex in pathorogical cardiac remodeling
| Project/Area Number |
18K15879
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 53020:Cardiology-related
|
|---|
| Research Institution | Akita University |
|---|
Principal Investigator |
SATO TERUKI 秋田大学, 医学部附属病院, 助教 (30733422)
|
|---|
| Project Period (FY) |
2018-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
|---|
| Keywords | CCR4-NOT複合体 / 心不全 / 心臓リモデリング |
|---|
| Outline of Final Research Achievements |
We investigated the functional role of CCR4-NOT deadenylase in pathological cardiac remodeling. Since protein X, a key factor of deadenylase, was upregulated in pressure overload-induced cardiac hypertrophy, we analyzed heart function of protein X KO mice which showed cardiac dysfunction and hypertrophy. RNA sequence revealed upregulation of inflammatory, cardiac hypertrophy and fibrosis associated genes. We thus focused on geneY, and generated protein X; gene Y double KO mice. Gene Y deficiency rescued cardiac dysfunction and hypertrophy of X KO mice with pressure overload. These results implicate that CCR4-NOT deadenylase negatively regulates cardiac remodeling induced by pressure overload via shortening of poly(A)tail of target mRNA.
|
| Academic Significance and Societal Importance of the Research Achievements |
心不全パンデミックと称されるように、今後心不全患者が増加することが予想されている。
有効な薬物療法やデバイス治療が開発されてきた一方で、いまだに心不全の予後は不良であるが、そこには心不全発症の分子病態解明が不十分であることから新規治療方法の開発が進まない背景がある。本研究では、RNA代謝制御に着目して、心臓リモデリングの病態解明を目的とした解析を行った。CCR4-NOT複合体は巨大なタンパク質複合体であり、生命維持に必須であることが分かっている。その機能的意義を解明することで、新たな心不全発症機序の解明やひいては治療法開発に貢献すると考えられる。
|
Report
(3 results)
Research Products
(12 results)
-
[Journal Article] B38-CAP is a bacteria-derived ACE2-like enzyme that suppresses hypertension and cardiac dysfunction2020
Author(s)
Minato T, Nirasawa S, Sato T, Yamaguchi T, Hoshizaki M, Inagaki T, Nakahara K, Yoshihashi T, Ozawa R, Yokota S, Natsui M, Koyota S, Yoshiya T, Yoshizawa-Kumagaye K, Motoyama S, Gotoh T, Nakaoka Y, Penninger JM, Watanabe H, Imai Y, Takahashi S, Kuba K
-
Journal Title
Nature Communications
Volume: 11(1)
Issue: 1
Pages: 1058-1058
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
-
