Abstract:
Skin wound healing is driven by proliferation, migration and differentiation of several cell types that are controlled by the alterations in the gene expression programmes. Brahma Gene 1 (BRG1) (also known as SMARCA4) is a core ATPase in the BRG1 Associated Factors (BAF) ATP-dependent chromatin remodelling complexes that alter DNA-histone interaction in chromatin at the specific gene regulatory elements resulting in increase or decrease of the target gene transcription. Using siRNA mediated suppression of BRG1 during wound healing in a human ex vivo and in vitro (scratch assay) models, we demonstrated that BRG1 is essential for efficient skin wound healing by promoting epidermal keratinocytes migration, but not their proliferation or survival. BRG1 controls changes in the expression of genes associated with gene transcription, response to wounding, cell migration and cell signalling. Altogether, our data revealed that BRG1 play positive role in skin repair by promoting keratinocyte migration and impacting the genes expression programmes associated with cell migration and cellular signalling.
摘要:
皮肤伤口愈合是由增殖驱动的,受基因表达程序改变控制的几种细胞类型的迁移和分化。Brahma基因1(BRG1)(也称为SMARCA4)是BRG1相关因子(BAF)ATP依赖性染色质重塑复合物中的核心ATPase,可在特定基因调控元件处改变染色质中的DNA-组蛋白相互作用,从而增加或减少目标基因转录。在人离体和体外(划痕试验)模型中,在伤口愈合期间使用siRNA介导的BRG1抑制,我们证明了BRG1通过促进表皮角质形成细胞的迁移对有效的皮肤伤口愈合至关重要,但不是它们的增殖或存活。BRG1控制与基因转录相关的基因表达的变化,对受伤的反应,细胞迁移和细胞信号。总之,我们的数据显示,BRG1通过促进角质形成细胞迁移和影响与细胞迁移和细胞信号相关的基因表达程序在皮肤修复中发挥积极作用.