2017 Fiscal Year Final Research Report
Mechanism and Biological Significance of Nucleolus-mediated Cell Fate Determination in Heart Failure
| Project/Area Number |
16K19418
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Cardiovascular medicine
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| Research Institution | Nara Medical University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Keywords | 心不全 / 細胞老化 / SASP / 核小体 / p53 / rRNA |
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| Outline of Final Research Achievements |
Recently, the contribution of p53 to many undesirable aspects of age-associated diseases, such as cardiovascular disorders, has been recognized. p53 induced-cellular senescence have been implicated heart failure. Therefore, we examined the role of nucleolus mediated-cellular senescence in heart failure. Transverse aortic constriction (TAC), model of pressure overload-induced heart failure, increased transcription of rRNA, expression of SASP factors and SA-B-gal positive senescent cells in failing heart. Moreover coculture experiments demonstrated that senescent cardiac fibroblasts induced by increasing nucleolar RNA content promoted hypertrophy of cardiomyocytes. Hypertrophy of cardiomyocytes is associated with heart failure. These results implied that nucleolus mediated-cellular senescence contribute to exacerbation of heart failure. Thus, modulation of the nucleolus may represent a novel approach for treatment of heart disease.
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| Free Research Field |
分子生物学
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