EZH2与Set7/9介导组蛋白甲基化在TGF-β1/Smads激活EGR1介导瘢痕疙瘩形成中的作用

瘢痕疙瘩（Keloid）作为一种持续性增生的病理性瘢痕，严重影响患者身心健康。课题组前期工作证实，TGF-β1/Smads是促使Keloid纤维化表型的最主要信号转导通路之一，该信号通路可激活EGR1，进而调控下游效应靶基因。鉴于EZH2和Set7/9对组蛋白H3甲基化修饰作用及H3K27me3与H3K4me1在纤维化进程中的重要表观遗传学调控作用。我们假设：TGF-β1/Smads激活EGR1是Keloid形成的关键分子机制；在此信号转导通路中，EZH2介导的H3K27me3和Set7/9介导的H3K4me1是TGF-β1/Smads信号转导和EGR1激活的关键调控因子。我们拟采用临床组织、差异表达细胞及动物模型，综合阐明Keloid形成过程中TGF-β1/Smads信号通路激活EGR1的分子机制及EZH2和Set7/9介导组蛋白甲基化的表观遗传学调控机制。

Keloid, as a pathological scar with persistent hyperplasia, seriously affects the physical and mental health of patients. Preliminary work of our research group confirmed that TGF-β1/Smads is one of the most important signal transduction pathways that promote keloid fibrosis phenotype, which can activate EGR1 and then regulate downstream target genes. In view of the effect of EZH2 and Set7/9 on the methylation modification of histone H3 and the important epigenetic regulation of H3K27me3 and H3K4me1 in the process of fibrosis, we hypothesized that TGF-β1/Smads activation of EGR1 is the key molecular mechanism of Keloid formation; In this signaling pathway, EZH2-mediated H3K27me3 and Set7/9-mediated H3K4me1 are key regulators of TGF-β1/Smads signal transduction and EGR1 activation. We intend to use clinical tissues, differentially expressed cells and animal models to comprehensively elucidate the regulation of chromatin remodeling of EGR1 activated by TGF-β1/Smads signaling pathway and the epigenetic regulation mechanism of EZH2 and Set7/9 mediated histone methylation during keloid formation.