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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 3

Adenovirus specifically infects supporting cells.

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Adenovirus specifically infects supporting cells.
Utricles were infected...
Utricles were infected with Ad-RFP for 2 hours and then cultured in control media for an additional 24 hours and fixed. Hair cells and supporting cells were visualized using myosin 7a (blue) and SOX2 (green) immunochemistry, respectively. Schematic shows the structure of the utricular sensory epithelium and the locations of the hair cells and supporting cells. Locations of confocal (optical) sections shown in the upper and lower panels are indicated by lines and arrows in the schematic. Upper panels: in confocal images taken at the level of the hair cell nuclei, the Ad-RFP signal appears in the spaces between hair cells and does not overlap with the hair cell marker myosin 7a. Lower panels: in confocal sections at the level of the supporting cell nuclei, the Ad-RFP signal colocalizes with the supporting cell marker SOX2. Ad-RFP infection results in RFP expression in supporting cells only, and no hair cells are infected. Scale bar: 20 μm.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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