Inhibition of apoptosis by survivin improves transplantation of pancreatic islets for treatment of diabetes in mice
Inhibition of apoptosis by survivin improves transplantation of pancreatic islets for treatment of diabetes in mice
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DOI：
10.1038/sj.embor.7400640
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发表时间：
2006-04-01
期刊：
影响因子：
7.7
通讯作者：
Altieri, DC
中科院分区：
文献类型：
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作者：
Dohi, T;Salz, W;Altieri, DC
存活素是一种参与抑制细胞凋亡和调节有丝分裂的癌基因，但其在正常细胞中的功能仍不清楚。在这里，我们发现在胰岛b细胞中表达生存素的转基因小鼠在细胞增殖方面没有变化，这是由胰岛大小或胰岛数量决定的。存活素转基因胰岛移植在糖尿病受体小鼠中提供长期植入和稳定纠正高血糖。这涉及体内对b细胞凋亡的内在抑制，以及胰岛中的整体转录变化，以及应激反应基因、细胞因子信号传导拮抗剂和血管生成促进剂的上调。生存素在体内广泛的细胞保护作用可能有助于糖尿病的基因治疗。
Survivin is a cancer gene implicated in inhibition of apoptosis and regulation of mitosis, but its function in normal cells has remained elusive. Here, we show that transgenic mice expressing survivin in pancreatic islet b-cells show no changes in cell proliferation, as determined by islet size or islet number. Transplantation of survivin transgenic islets in diabetic recipient mice affords long-term engraftment and stable correction of hyperglycaemia. This involves intrinsic inhibition of b-cell apoptosis, in vivo, and global transcriptional changes in pancreatic islets with upregulation of stress response genes, antagonists of cytokine signalling and promoters of angiogenesis. These broad cytoprotective functions of survivin in vivo might be beneficial for gene therapy of diabetes.