Inhibition of apoptosis by survivin improves transplantation of pancreatic islets for treatment of diabetes in mice

被引:32
作者
Dohi, T
Salz, W
Costa, M
Ariyan, C
Basadonna, GP
Altieri, DC [1 ]
机构
[1] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA
[2] Univ Massachusetts, Sch Med, Ctr Canc, Worcester, MA 01605 USA
[3] Univ Massachusetts, Sch Med, Dept Surg, Worcester, MA 01605 USA
[4] Yale Univ, Sch Med, Dept Surg, New Haven, CT 06510 USA
关键词
survivin; apoptosis; pancreatic islets; transplantation; gene expression;
D O I
10.1038/sj.embor.7400640
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
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.
引用
收藏
页码:438 / 443
页数:6
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