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Protective role of the inhibitor of apoptosis protein, survivin, in toxin-induced acute renal failure

VIB Department of Transgene Technology and Gene Therapy, K.U. Leuven, Leuven, Belgium

¹Correspondence: Center for Transgene Technology and Gene Therapy, Flanders Institute for Biotechnology, University of Leuven, Herestraat 49, B-3000 Leuven, Belgium. E-mail: ed.conway{at}med.kuleuven.be

Acute renal failure (ARF) is a major worldwide cause of morbidity and mortality, lacking specific targeted, effective therapies. Renal tubular cell apoptosis has been recognized to play a critical role in the pathogenesis of ARF, yet few studies have evaluated whether intervention in apoptotic pathways can ameliorate the deterioration in renal function associated with ARF. Using transgenic mice with diminished levels of the inhibitor of apoptosis protein, survivin, we show that survivin is required to protect the kidney from apoptosis, to suppress renal expression of p53, and to ameliorate renal dysfunction in two models of ARF. Gene delivery of survivin to wild-type mice and mice with 50% levels of survivin, prior to or at the time of induction of ARF, interferes with the deterioration of renal function and preserves the integrity of the kidneys and the renal tubular cells by inhibiting activation of apoptotic pathways in the kidneys and suppressing expression of p53. These results encourage further evaluation of survivin, its active structural domains, and other inhibitors of apoptosis proteins, for preventing and/or treating acute renal failure.—Kindt, N., Menzebach, A., Van de Wouwer, M., Betz, I., De Vriese, A., Conway, E. M. Protective role of the inhibitor of apoptosis protein, survivin, in toxin-induced acute renal failure.

Key Words: caspase • cisplatin • kidney • transgenic mice • p53 • hydrodynamic gene therapy