Exosomes mediate sensory hair cell protection in the inner ear
Hair cells, the mechanosensory receptors of the inner ear, are responsible for hearing and balance. Hair cell death and consequent hearing loss are common results of treatment with ototoxic drugs, including the widely used aminoglycoside antibiotics. Induction of heat shock proteins (HSPs) confers p...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
American Society for Clinical Investigation
2020
|
| _version_ | 1797106654331797504 |
|---|---|
| author | Breglio, AM May, LA Barzik, M Welsh, NC Francis, SP Costain, TQ Wang, L Anderson, ED Petralia, RS Wang, YX Friedman, TB Wood, MJA Cunningham, LL |
| author_facet | Breglio, AM May, LA Barzik, M Welsh, NC Francis, SP Costain, TQ Wang, L Anderson, ED Petralia, RS Wang, YX Friedman, TB Wood, MJA Cunningham, LL |
| author_sort | Breglio, AM |
| collection | OXFORD |
| description | Hair cells, the mechanosensory receptors of the inner ear, are responsible for hearing and balance. Hair cell death and consequent hearing loss are common results of treatment with ototoxic drugs, including the widely used aminoglycoside antibiotics. Induction of heat shock proteins (HSPs) confers protection against aminoglycoside-induced hair cell death via paracrine signaling that requires extracellular heat shock 70-kDa protein (HSP70). We investigated the mechanisms underlying this non–cell-autonomous protective signaling in the inner ear. In response to heat stress, inner ear tissue releases exosomes that carry HSP70 in addition to canonical exosome markers and other proteins. Isolated exosomes from heat-shocked utricles were sufficient to improve survival of hair cells exposed to the aminoglycoside antibiotic neomycin, whereas inhibition or depletion of exosomes from the extracellular environment abolished the protective effect of heat shock. Hair cell–specific expression of the known HSP70 receptor TLR4 was required for the protective effect of exosomes, and exosomal HSP70 interacted with TLR4 on hair cells. Our results indicate that exosomes are a previously undescribed mechanism of intercellular communication in the inner ear that can mediate nonautonomous hair cell survival. Exosomes may hold potential as nanocarriers for delivery of therapeutics against hearing loss. |
| first_indexed | 2024-03-07T07:05:38Z |
| format | Journal article |
| id | oxford-uuid:037e7b32-0e63-4c0b-9dc3-b1f48f7f8b92 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:05:38Z |
| publishDate | 2020 |
| publisher | American Society for Clinical Investigation |
| record_format | dspace |
| spelling | oxford-uuid:037e7b32-0e63-4c0b-9dc3-b1f48f7f8b922022-05-09T10:25:05ZExosomes mediate sensory hair cell protection in the inner earJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:037e7b32-0e63-4c0b-9dc3-b1f48f7f8b92EnglishSymplectic ElementsAmerican Society for Clinical Investigation 2020Breglio, AMMay, LABarzik, MWelsh, NCFrancis, SPCostain, TQWang, LAnderson, EDPetralia, RSWang, YXFriedman, TBWood, MJACunningham, LLHair cells, the mechanosensory receptors of the inner ear, are responsible for hearing and balance. Hair cell death and consequent hearing loss are common results of treatment with ototoxic drugs, including the widely used aminoglycoside antibiotics. Induction of heat shock proteins (HSPs) confers protection against aminoglycoside-induced hair cell death via paracrine signaling that requires extracellular heat shock 70-kDa protein (HSP70). We investigated the mechanisms underlying this non–cell-autonomous protective signaling in the inner ear. In response to heat stress, inner ear tissue releases exosomes that carry HSP70 in addition to canonical exosome markers and other proteins. Isolated exosomes from heat-shocked utricles were sufficient to improve survival of hair cells exposed to the aminoglycoside antibiotic neomycin, whereas inhibition or depletion of exosomes from the extracellular environment abolished the protective effect of heat shock. Hair cell–specific expression of the known HSP70 receptor TLR4 was required for the protective effect of exosomes, and exosomal HSP70 interacted with TLR4 on hair cells. Our results indicate that exosomes are a previously undescribed mechanism of intercellular communication in the inner ear that can mediate nonautonomous hair cell survival. Exosomes may hold potential as nanocarriers for delivery of therapeutics against hearing loss. |
| spellingShingle | Breglio, AM May, LA Barzik, M Welsh, NC Francis, SP Costain, TQ Wang, L Anderson, ED Petralia, RS Wang, YX Friedman, TB Wood, MJA Cunningham, LL Exosomes mediate sensory hair cell protection in the inner ear |
| title | Exosomes mediate sensory hair cell protection in the inner ear |
| title_full | Exosomes mediate sensory hair cell protection in the inner ear |
| title_fullStr | Exosomes mediate sensory hair cell protection in the inner ear |
| title_full_unstemmed | Exosomes mediate sensory hair cell protection in the inner ear |
| title_short | Exosomes mediate sensory hair cell protection in the inner ear |
| title_sort | exosomes mediate sensory hair cell protection in the inner ear |
| work_keys_str_mv | AT breglioam exosomesmediatesensoryhaircellprotectionintheinnerear AT mayla exosomesmediatesensoryhaircellprotectionintheinnerear AT barzikm exosomesmediatesensoryhaircellprotectionintheinnerear AT welshnc exosomesmediatesensoryhaircellprotectionintheinnerear AT francissp exosomesmediatesensoryhaircellprotectionintheinnerear AT costaintq exosomesmediatesensoryhaircellprotectionintheinnerear AT wangl exosomesmediatesensoryhaircellprotectionintheinnerear AT andersoned exosomesmediatesensoryhaircellprotectionintheinnerear AT petraliars exosomesmediatesensoryhaircellprotectionintheinnerear AT wangyx exosomesmediatesensoryhaircellprotectionintheinnerear AT friedmantb exosomesmediatesensoryhaircellprotectionintheinnerear AT woodmja exosomesmediatesensoryhaircellprotectionintheinnerear AT cunninghamll exosomesmediatesensoryhaircellprotectionintheinnerear |