同型半胱氨酸(Hcy)是终末期肾病的独立危险因子，但其致病机制未清。课题组前期观察到DNA甲基化是Hcy致肾损伤的重要机制，且预实验结果提示miRNAs参与了肾损伤的调控。而组蛋白甲基化具有招募转录因子协同DNA甲基化调控基因转录的作用，故我们推测：Hcy经转录因子c-myc协同H3K27甲基化沉默特异性miRNAs是肾损伤的重要机制。为了验证该假说，首先探讨c-myc在Hcy致肾损伤中的作用；运用微阵列等技术筛选并确定其特异性miRNAs(miR-92a)，构建c-myc重组和干扰质粒转染足细胞，明确c-myc与miR-92a的相互调控关系；使EZH2和c-myc沉默和过表达载体并转染，分析miR-92a启动子区甲基化水平，阐明c-myc结合到miR-92a启动子区并募集EZH2催化H3K27me3致miR-92a沉默的表观遗传学分子机制，寻找关键靶点，为防治Hcy致肾损伤提供新策略。

Homocysteine (Hcy)，which served as an independent risk factor of renal damage, the pathogenic mechanism is still unkown. Our previous study proved that DNA methylation is an important mechanism of Hcy-induced renal damage, and the pre-experimental results suggested that miRNAs is involved in the regulation of renal damage . The histone methylation plays an important role in recruiting transcription factors to regulate gene transcription cooperating with DNA methylation .Then，the hypothesis we will propose like this: Hcy via transcription factor c-myc which coordinate with H3K27 methylation to silence specific miRNAs is the significant mechanism in renal damage. In order to vertify this hypothesis , to define the role of c-myc in renal damage induced by Hcy; To clarify the interrelation of c-myc and miR-92a, screene and identify the specific miRNAs(miR-92a) by the channel of the microarray technology, construct the recombinant and inference plasmid of transcription factor c-myc to transfecte the podocyte ; Silence and overexpress EZH2 ,c-myc, analysis the level of methylation of miR-92a promoter region, to confirm the epigenetic mechanisms of c-myc combine the promoter region of miR-92a then catalysis H3K27me3 by recruiting EZH2 to silence miR-92a .In this way, we will seek the essential target, and provide a new strategy for the prevention and curement of Hcy-induced renal damage.