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 8

Exogenous HSP70 is protective.

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Exogenous HSP70 is protective. (A) Utricles were cultured in neomycin wi...
(A) Utricles were cultured in neomycin with (or without) recombinant human HSP70. Recombinant HSA was used as a control. Neomycin resulted in significant loss of hair cells (ANOVA, *P < 0.05 relative to control). Addition of exogenous HSP70 inhibited neomycin-induced hair cell death (ANOVA, #P < 0.05 relative to neomycin), while HSA was not protective. n = 5–20 utricles per condition. (B) Exogenous HSP70 is not internalized by hair cells. Neomycin-treated utricles were cultured in the presence of FITC-labeled recombinant human HSP70 (ExHSP70-FITC) or BSA (ExBSA-FITC) and examined for the presence of intracellular HSP70-FITC (or BSA-FITC) (green). Hair cells were labeled with an antibody against myosin 7a (red). Neither ExHSP70-FITC nor ExBSA-FITC was internalized by hair cells, although supporting cells internalized small amounts of both exogenous proteins. Scale bar: 10 μm (applies to all panels). Orth, orthogonal.