Inhibition of apoptosis by survivin improves transplantation of pancreatic islets for treatment of diabetes in mice.
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 beta-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 beta-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.
Department of Cancer Biology, University of Massachusetts Medical School, Worcester, 01605, USA.
Takehiko
T
Dohi
Whitney
W
Salz
Marco
M
Costa
Charlotte
C
Ariyan
Giacomo P
GP
Basadonna
Dario C
DC
Altieri
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000601:surgery*; D005786:Gene Expression Regulation; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007515:Islets of Langerhans / Q000473:pathology* / Q000601:surgery; D016381:Islets of Langerhans Transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D012097:Repressor Proteins; D000077022:Survivin
C107489:BIRC5 protein, human; C117749:Birc5 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D012097:Repressor Proteins; D000077022:Survivin