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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

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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 6

HSP70 is secreted to the medium, and depletion of HSP70 from the medium abolishes the protective effect of coculture.

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HSP70 is secreted to the medium, and depletion of HSP70 from the medium ...
(A) HSP70 levels in medium from control and heat-shocked utricles were examined by ELISA. Medium surrounding heat-shocked utricles contained significantly more HSP70 than medium surrounding the control (nonheat-shocked) utricles (ANOVA, P < 0.0005). HSP70 levels in control tissue were comparable to those in control medium, while heat-shocked utricles contained significantly higher levels of HSP70. Shown are data from 3 biological replicates processed in parallel. The experiment was repeated 5 times with similar results. (B) Heat-shocked (upper chamber) and nonheat-shocked (lower chamber) utricles from Hsp70+/+ mice were cocultured in a Transwell device containing 5 mM of gentamicin. As in Figure 5, gentamicin resulted in significant hair cell death, and both heat-shocked (upper) and nonheat-shocked (cocultured, lower) utricles were protected. Addition of a control IgG to the medium did not alter the protective effect of either heat shock (upper) or coculture with heat-shocked (lower) utricles. Depletion of HSP70 from the medium using an HSP70 function-blocking antibody (fbAb) abolished the protective effect of both heat-shocked (upper) and nonheat-shocked, cocultured (lower) utricles. ANOVA, *P < 0.05 relative to gentamicin. n = 5–15 utricles per condition.

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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