Epigenetic regulation of gene expression related to compensated myocardial hypertrophy under pressure overload

压力超负荷下代偿性心肌肥大相关基因表达的表观遗传调控

• 批准号: 22790720
• 负责人: HONSHOU Shouken
• 金额: $ 2.58万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22790720/
• 关键词: 心筋肥大; プロモーター; メチル化; IL-1; IGF-1; エピジェネティクス; DNAメチル化

The mechanism of disruption of compensated myocardial hypertrophy under excessive pressure overload has not been fully clarified. We previously described that low level of IL-1 is constitutively produced and IL-1 induce IGF-1 to maintain homeostasis of cardiomyocyte under pressure overload. In this report, we addressed the epigenetic regulatory mechanism to control expression of genes which is involved in the transition of compensated hypertrophy to dilated heart failure. As a result, during the transition phase of compensated hypertrophy to decompensated dilated heart failure, methylation of IGF-1 promoter was increased. Furthermore, in vivo administration of DNA methyl-transferase inhibitors increases expression level of IGF-1 and inhibited transition of compensated hypertrophy to dilated heart failure.

过度压力超负荷下代偿性心肌肥大的破坏机制尚未完全阐明。我们之前描述过，低水平的IL-1是组成性产生的，IL-1诱导IGF-1在压力超负荷下维持心肌细胞的稳态。在本报告中，我们探讨了表观遗传调控机制，以控制参与代偿性肥大向扩张性心力衰竭转变的基因表达。结果，在代偿性肥大向失代偿性扩张性心力衰竭的过渡阶段，IGF-1启动子的甲基化增加。此外，体内给予DNA甲基转移酶抑制剂可增加IGF-1的表达水平并抑制代偿性肥大向扩张性心力衰竭的转变。