心脏重构是心肌肥厚等心血管疾病导致心力衰竭发生发展的核心机制。阐明心脏重构的分子机理对于防治心衰具有重要的意义。干扰素调节因子（IRF）家族是天然免疫网络中的核心转录因子家族。我们过去一系列的研究显示，IRF家族众多成员可以通过非免疫细胞依赖的方式调节心肌肥厚及其引起的心力衰竭的发生发展。IRF5和IRF6虽然与IRF家族其他成员同源性较高，但是它们的功能却显著不同。IRF5特异性调控免疫细胞成熟分化和自身免疫性疾病发生，而IRF6则与天然免疫并无关系，主要与角质细胞的分化有关。进一步研究发现IRF5、IRF6的表达在压力负荷诱导的心肌肥厚中显著升高。然而，IRF5、IRF6是否调控心肌肥厚引起的心力衰竭尚不清楚。本项目结合前期工作，拟通过心肌细胞特异性IRF5、IRF6基因敲除和转基因小鼠模型，结合大规模筛选技术手段，阐明IRF5、IRF6在心肌肥厚及其引起的心力衰竭中的功能和作用机制。

Cardiac remodeling is critical for the formation and development of heart failure induced by cardiovascular diseases such as hypertrophy. Thus, a thorough understanding of the mechanism of cardiac remodeling will be helpful for prevention and therapy of heart failure. Interferon regulatory factors (IRFs) are key transcription factor family of innate immune network. Our previous studies showed that certain members of IRFs modulated cardiac hypertrophy and heart failure through an immune-cell independent manner. Although IRF5 and IRF6 have high similarity with the other IRF members, they have different functions compared with them. IRF5 specifically regulates immune cell differentiation and maturation, whereas IRF6 has no relationship with innate immune, it mainly involves in the keratinocyte proliferation and differentiation. Our further research revealed that the expression of IRF5 and IRF6 was significantly increased in the heart after pressure overload. However, whether IRF5 and IRF6 regulate cardiac hypertrophy and heart failure is still unknown. Based on our preliminary studies, using cardiomyocyte specific IRF5/IRF6 gene knockout or transgenic mice as well as high throughput technology, we plan to elucidate the effect and underlying mechanism of IRF5/IRF6 on cardiac hypertrophy and heart failure.