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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., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Deletion of Fscn2 gene in mice has been linked to progressive hearing loss and degeneration of cochlear cells. Cisplatin, an antitumor drug, can cause various side effects, including ototoxicity. The aim of this study was to investigate the effects of Fscn2 on cisplatin-induced hearing impairment in mice and to explore the possible mechanism. Methods: Two-week-old Fscn2+/+ mice and Fscn2−/− mice were treated with two doses of cisplatin, with a 3-day recovery period in between. ABR (auditory evoked brain stem response) thresholds were measured and cochlear pathology was observed at 3 weeks of age. Results: Both Fscn2+/+ and Fscn2−/− mice showed hearing loss under the effect of cisplatin, but the impairment was more severe in Fscn2−/− mice. Further experiments showed that the percentages of outer hair cell (OHC) and spiral ganglion neuron (SGN) loss were significantly higher in cisplatin-treated Fscn2−/− mice compared to Fscn2+/+ mice. Additionally, knockdown of Fscn2 in HEI-OC1 cells worsened cisplatin-induced cell apoptosis. Conclusion: FSCN2 mediates reduction of CDDP induced ototoxicity by inhibiting cell apoptosis.