Article ID Journal Published Year Pages File Type
5562202 Toxicology Letters 2017 9 Pages PDF
Abstract

•Cisplatin induces loss of fascin2 protein expression in vitro and in vivo.•Fascin2 is regulated, in part, by α(E)-catenin.•Knockdown of fascin2 increases susceptibility to cisplatin nephrotoxicity in vitro.•Overexpression of fascin2 is renoprotective against cisplatin injury in vitro.

Previous studies have shown that the aging kidney has a marked loss of α(E)-catenin in proximal tubular epithelium. α-Catenin, a key regulator of the actin cytoskeleton, interacts with a variety of actin-binding proteins. Cisplatin-induced loss of fascin2, an actin bundling protein, was observed in cells with a stable knockdown of α(E)-catenin (C2 cells), as well as in aging (24 mon), but not young (4 mon), kidney. Fascin2 co-localized with α-catenin and the actin cytoskeleton in NRK-52E cells. Knockdown of fascin2 increased the susceptibility of tubular epithelial cells to cisplatin-induced injury. Overexpression of fascin2 in C2 cells restored actin stress fibers and attenuated the increased sensitivity of C2 cells to cisplatin-induced apoptosis. Interestingly, fascin2 overexpression attenuated cisplatin-induced mitochondrial dysfunction and oxidative stress in C2 cells. These data demonstrate that fascin2, a putative target of α(E)-catenin, may play important role in preventing cisplatin-induced acute kidney injury.

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Life Sciences Environmental Science Health, Toxicology and Mutagenesis
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