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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 9

Ad-HSP70-mCherry is protective, and it is not internalized by hair cells.

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Ad-HSP70-mCherry is protective, and it is not internalized by hair cells...
(A) Supporting cells were infected with Ad-HSP70-mCherry (or Ad-mCherry as a control). Infected utricles were cultured in the presence or absence of neomycin (3 mM). Neither virus resulted in significant hair cell death, while neomycin caused a significant loss of hair cells. Infection of supporting cells with Ad-HSP70-mCherry inhibited neomycin-induced hair cell death (ANOVA, *P < 0.05). Infection of supporting cells with Ad-mCherry was not protective. n = 6–11 utricles per condition. (B) Utricles infected with Ad-HSP70-mCherry were fixed, and hair cells were labeled using antimyosin 7a (green). Utricles were examined using confocal microscopy (original magnification, ×63). Schematic shows the location of each panel. Upper panels show confocal images taken at the level of the hair cell cuticular plates, while the lower panels show confocal images from the same field taken at the level of the hair cell nuclei. Ad-HSP70-mCherry (red) is restricted to supporting cells and does not colocalize with myosin 7a (green, hair cells), indicating that Ad-HSP70-mCherry does not translocate from supporting cells to hair cells. Scale bars: 20 μm.

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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