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Protective role of the inhibitor of apoptosis protein, survivin, in toxin‐induced acute renal failure
Author(s) -
Kindt Nele,
Menzebach Axel,
Van de Wouwer Marlies,
Betz Inge,
De Vriese Astrid,
Conway Edward M.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.07-8882com
Subject(s) - survivin , apoptosis , kidney , inhibitor of apoptosis , medicine , cancer research , renal function , pathogenesis , acute kidney injury , pharmacology , programmed cell death , biology , cancer , biochemistry
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. FASEB J. 22, 510–521 (2008)