| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Outline of Final Research Achievements |
Smooth muscle cells (SMCs) play a pivotal role in development of vascular disease, in which they markedly change their phenotypes. We established a novel in vitro SMC differentiation system using iPS cells. Using this system we assessed if histone modifying enzymes (HMEs) might be involved in SMC differentiation and phenotypic modulation. We found a number of HMEs were differentially regulated during SMC differentiation. We also found that expression of many HMEs was altered in phenotypically modulated SMCs in the mouse carotid ligation model. Based on these results we identified 10 HMEs that might be involved in the control of SMC phenotype and systematically knocked down them in SMCs. Among the HMEs tested HME-A was upregulated by phenotypic modulation and its knockdown markedly augmented the SMC differentiation marker genes, suggesting that HME-A is crucially involved in phenotypic modulation of SMCs.
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