2006 Fiscal Year Final Research Report Summary
Study of molecular mechanism of cardiomyocyte cell cycle and heart regeneration
| Project/Area Number |
17590712
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
ADACHI Mimi Tokyo Medical and Dental University, Medical Research Institute, Assistant Professor, 難治疾患研究所, 助手 (10323693)
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| Project Period (FY) |
2005 – 2006
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| Keywords | cardiomyocyte / proliferation / cyclin D1 / p27^<kip1> / Skp2 |
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| Research Abstract |
Mammalian cardiomyocytes are terminally differentiated and do not proliferated in adults. Recently we have reported that expression of cyclin D1 tagged with a nuclear localization signal (D1NLS) and Skp2, which is ubiquitin E3 ligase for p27, allows cardiomyocytes to re-enter cell cycle. It has remained unknown, however, if such cardiomyocytes undergo normal cell division. In this study, we show that cardiomyocytes in culture expressing D1NLS/CDK4 and Skp2 upregulate G1, S, and G2M cyclins, regulators of DNA replication (Orc6 and Geminin), and also CDK inhibitors (INK4 and CIP.KIP family). In a rat myocardial infarction model, D1NLS, CDK4, Skp2 induce an indicator of S phase (Ki67), M phase (phosphorylated histone H3), and cytokinesis (Aurora B/Survivin). These data demonstrate that mammalian cardiomyocytes can be induced to undergo complete cell division in vivo through acceleration (D1NLS/CDK4) and release from breakes (Skp2) of cell cycle. These findings have clinical implications since expression of D1NLS/CDK4 and Skp2 reduces the size of infarction and improves parameters of left ventricular function and lung homeostasis. Thus, in situ proliferation of adult cardiomyocytes may provide a novel therapeutic approach for prevention and treatment of heart failure.
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Research Products
(12 results)
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[Journal Article] Induction of apoptosis and cellular senescence in mice lacking transcription elongation factor, Elongin A.2007
Author(s)
Miyata Y, Yasukawa T, Fukuda M, Takeuchi T, Yamazak K, Sakumi K, Tamamori-Adachi M, Ohnishi Y, Ohtsuki Y, Nakabeppu Y, Kiatjima S, Aso T
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Journal Title
Cell Death and Differentiation 14
Pages: 716-726
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Stress response gene ATF3 is a target of c-myc is serum-induced cell proliferation.2005
Author(s)
Tamura K, Bayin H, Adachi S, Guney I, Kawauchi J, Morioka M, Tamamori-Adachi M, Tanaka Y, Nakabeppu Y, Sunamori M, Sedivy JM, Kitajima S
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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