2017 Fiscal Year Final Research Report
Enhancement of the endogeneous cardiac regeneration via activation of Hippo-YAP signaling pathway
| Project/Area Number |
15K09132
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Cardiovascular medicine
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2015-04-01 – 2018-03-31
|
| Keywords | 創薬 / 心筋再生 / 心筋細胞分裂 / Hippo-YAP経路 / 心筋梗塞 / 心不全 |
|---|
| Outline of Final Research Achievements |
Accumulating data suggest that new cardiomyocytes in adults are generated from existing cardiomyocytes throughout life. To enhance the endogenous cardiac regeneration, we performed chemical screenings to identify compounds that activate pro-proliferative YAP and TEADs activities in cardiomyocytes. We synthesized a novel fluorine-containing TT-10 (C11H10FN3OS2) from the biologically hit compound. TT-10 promoted cardiomyocyte proliferation and simultaneously exerted anti-oxidant and anti-apoptotic effects in vitro. TT-10 treatment in mice ameliorated myocardial infarction-induced cardiac dysfunction at least in part via enhancing clonal expansion of existing cardiomyocytes. Stimulating cardiomyocyte proliferation and/or protection with TT-10 might complement current therapies for myocardial infarction.
|
| Free Research Field |
医歯薬学
|
