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首页> 外文期刊>European Journal of Translational Myology >Proliferating myoblasts transfected with FasL cDNA can escape from apoptosis
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Proliferating myoblasts transfected with FasL cDNA can escape from apoptosis

机译：FasL cDNA转染的增生成肌细胞可逃避凋亡

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An important but all too often neglected aspect of successful gene therapy is the attenuation or elimination of the local inflammatory response and immune reaction against transferred DNA products and cell transplantation. Expression of the FasL protein, either constitutively or after induction in certain cells, induces apoptosis when it interacts with the Fas cell-surface receptor (APO1, CD95) and the interaction Fas-FasL on T cells is thought to play a major role in the maintenance of immunological homeostasis and peripheral tolerance. Recently attention has focused on the creation of loci of immune privilege (FasL overexpressing loci) where transfected cells can be placed. During attempts to produce myotubes expressing the apoptosis-inducing FasL protein under the control of a CMV promoter, mainly myoblasts were unable to survive the initial transfection. Investigation of the presence of Fas led us to determine that the mRNA for Fas is upregulated during differentiation program of myoblasts corresponding to the peak of cell death in transfected cells. When the cultures are prolonged, some myoblasts can survive and proliferate and are able to form some FasL positive myotubes. Our findings shed light on the conflicting results obtained by two recent studies on FasL engineered myoblasts and open new perspectives regarding the possibility to induce forced expression of FasL in muscle cells.
机译：成功的基因治疗的一个重要但经常被忽视的方面是减弱或消除了针对转移的DNA产物和细胞移植的局部炎症反应和免疫反应。 FasL蛋白的表达（在某些细胞中组成性或诱导后）在与Fas细胞表面受体（APO1，CD95）相互作用时诱导凋亡，而Fas-FasL在T细胞上的相互作用被认为在其中起主要作用。维持免疫稳态和外周耐受性。近来，注意力集中在可建立转染细胞的免疫特权基因座（FasL过表达基因座）上。在尝试产生在CMV启动子控制下表达诱导凋亡的FasL蛋白的肌管的过程中，主要是成肌细胞不能在最初的转染中存活。对Fas存在的研究使我们确定，在成肌细胞分化程序中，与转染细胞中细胞死亡的峰值相对应的Fas mRNA上调。当培养时间延长时，一些成肌细胞可以存活和增殖，并能够形成一些FasL阳性肌管。我们的发现揭示了最近两项有关FasL改造成肌细胞的研究的相互矛盾的结果，并就诱导FasL在肌肉细胞中强迫表达的可能性开辟了新的视角。

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