Inner ear supporting cells protect hair cells by secreting HSP70
Lindsey A. May, … , Fu-Shing Lee, Lisa L. Cunningham
Lindsey A. May, … , Fu-Shing Lee, Lisa L. Cunningham
Published July 25, 2013
Citation Information: J Clin Invest. 2013;123(8):3577-3587. https://doi.org/10.1172/JCI68480.
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Research Article

Inner ear supporting cells protect hair cells by secreting HSP70

Abstract

Mechanosensory hair cells are the receptor cells of hearing and balance. Hair cells are sensitive to death from exposure to therapeutic drugs with ototoxic side effects, including aminoglycoside antibiotics and cisplatin. We recently showed that the induction of heat shock protein 70 (HSP70) inhibits ototoxic drug–induced hair cell death. Here, we examined the mechanisms underlying the protective effect of HSP70. In response to heat shock, HSP70 was induced in glia-like supporting cells but not in hair cells. Adenovirus-mediated infection of supporting cells with Hsp70 inhibited hair cell death. Coculture with heat-shocked utricles protected nonheat-shocked utricles against hair cell death. When heat-shocked utricles from Hsp70–/– mice were used in cocultures, protection was abolished in both the heat-shocked utricles and the nonheat-shocked utricles. HSP70 was detected by ELISA in the media surrounding heat-shocked utricles, and depletion of HSP70 from the media abolished the protective effect of heat shock, suggesting that HSP70 is secreted by supporting cells. Together our data indicate that supporting cells mediate the protective effect of HSP70 against hair cell death, and they suggest a major role for supporting cells in determining the fate of hair cells exposed to stress.

Authors

Lindsey A. May, Inga I. Kramarenko, Carlene S. Brandon, Christina Voelkel-Johnson, Soumen Roy, Kristy Truong, Shimon P. Francis, Elyssa L. Monzack, Fu-Shing Lee, Lisa L. Cunningham

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Figure 5

Coculture with heat-shocked utricles is protective.

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Coculture with heat-shocked utricles is protective. Utricles were cultur...
Utricles were cultured in 24-well plates containing Transwell permeable inserts. For each experiment, heat-shocked utricles were placed in the upper chamber of the Transwell device, and nonheat-shocked utricles were placed in the lower chamber. (A) Wild-type (Hsp70+/+) utricles were cocultured. Control utricles and heat-shocked utricles had comparable hair cell densities. Gentamicin caused significant loss of hair cells. Heat-shocked utricles (upper chamber) were partially protected against gentamicin-induced hair cell death. Nonheat-shocked utricles (bottom chamber) were protected in a manner comparable to heat-shocked utricles. (B) When utricles from Hsp70–/– mice were used in both chambers (heat-shocked and nonheat-shocked), protection against gentamicin-induced hair cell death was abolished in both groups of utricles. (C) Hsp70–/– utricles were heat shocked and cultured in the upper chamber of the Transwell device, while Hsp70+/+ utricles (nonheat shocked) were in the lower chamber. No protective effect against gentamicin-induced hair cell death was observed in either group. (D) Hsp70+/+ utricles were heat shocked and cultured in the upper chamber of the Transwell device, while Hsp70–/– utricles (nonheat shocked) were in the lower chamber. Both groups were protected against gentamicin-induced hair cell death. ANOVAs, *P < 0.05. n = 5–11 utricles per condition. Gent, gentamicin; HS, heat shocked.