Autophagy: A Novel Horizon for Hair Cell Protection

Liu, Chang; Zheng, Zhiwei; Wang, Pengjun; He, Shuangba; He, Yingzi

doi:10.1155/2021/5511010

Cited by 8 publications

(8 citation statements)

References 148 publications

(170 reference statements)

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“…Interestingly, studies have shown that promoting lysosomal delivery through autophagy of aminoglycosides is cytoprotective [37]. Recently, autophagy has emerged as a potential target for treating various SNHL by decreasing oxidative stress levels and apoptosis [13,14]. In our experiments, the results show that MSC-derived exosomes can markedly activate autophagy both in the normal basal state and upon neomycin-induced damage conditions in hair cells.…”

Section: Discussionmentioning

confidence: 54%

“…Autophagy has been demonstrated to be a core pathway for the preservation of cellular and organismal homeostasis, which is tightly involved in hair cell protection [13,14,25]. Therefore, we explored whether autophagy in hair cells could be enhanced by exosomes.…”

Section: Resultsmentioning

confidence: 99%

“…Autophagy is an evolutionarily conserved system for the degradation of cytoplasmic elements and plays a pivotal role in the quality control of proteins and organelles [35,36]. Autophagy is particularly important in the inner ear, which consists of terminally differentiated cells with very limited regenerative ability in neonatal ages and completely loses its regenerative capacity in adults [13,14]. This restriction of spontaneous hair cell regeneration attributes to the fact that the hearing ability is not able to recover once hair cells are damaged [3].…”

Section: Discussionmentioning

confidence: 99%

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MSC-derived exosomes protect auditory hair cells from neomycin-induced damage via autophagy regulation

Liu

Kuang

Wang

et al. 2023

Preprint

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Increasing incidence of sensorineural hearing loss (SNHL) has raised concerns over the disease, while the limited treatment options have motivated the study of new biological therapies. Among these, mesenchymal stem cell (MSC) transplantation has been shown to improve hearing function, and accumulating evidence indicates that MSCs could impart their therapeutic effects by secreting exosomes. However, the underlying therapeutic mechanisms are not fully understood. Herein, in a neomycin-induced SNHL model, we found that exosomes released by MSCs rescued hearing loss and ameliorated hair cell loss by regulating autophagy of the recipient hair cells. Mechanistically, exogenous exosomes could be engulfed by hair cells after treatment. Then, in the hair cells, exosomes promoted the expression of endocytic genes and the formation of endosomes, thus inducing autophagy activation. Finally, the enhanced autophagy promoted cell survival, reduced mitochondrial oxidative stress and apoptosis of hair cells, and attenuated neomycin-induced ototoxic damage. Collectively, our study unveiled the otoprotective role of autophagy activated by exogenous exosomes in hair cells, and verified the potential of extracellular vesicle-based biological therapy for SNHL caused by neomycin.

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Section: Discussionmentioning

confidence: 54%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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MSC-derived exosomes protect auditory hair cells from neomycin-induced damage via autophagy regulation

Liu

Kuang

Wang

et al. 2023

Preprint

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“…Overall, research on the role played by autophagy in hearing loss is in an emergent phase (He et al, 2018;Ye et al, 2018;Fu and Chai, 2019;Guo et al, 2021;Liu C. et al, 2021). Certainly, more investigation into various auditory cells, including nonsensory cells, is needed to determine the autophagic function in specific cells involved hearing loss.…”

Section: Discussionmentioning

confidence: 99%

Cellular autophagy, the compelling roles in hearing function and dysfunction

Wan

Zhang

Hua

2022

Front. Cell. Neurosci.

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Sensorineural hearing loss (SNHL) is currently a major health issue. As one of the most common neurodegenerative diseases, SNHL is associated with the degradation of hair cells (HCs), spiral ganglion neurons (SGNs), the stria vascularis, supporting cells and central auditory system cells. Autophagy is a highly integrated cellular system that eliminates impaired components and replenishes energy to benefit cellular homeostasis. Etiological links between autophagy alterations and neurodegenerative diseases, such as SNHL, have been established. The hearing pathway is complex and depends on the comprehensive functions of many types of tissues and cells in auditory system. In this review, we discuss the roles of autophagy in promoting and inhibiting hearing, paying particular attention to specific cells in the auditory system, as discerned through research. Hence, our review provides enlightening ideas for the role of autophagy in hearing development and impairment.

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“…On the other hand, autophagy can remove damaged organelles, defend against microbial infection, and has a protective effect against metabolic, heart disease, and neurodegenerative diseases (including Parkinson's, Alzheimer's, and Huntington's) (Yu et al, 2004). In hair cells, autophagy plays an important role in preventing ototoxicity, including aminoglycoside-, cisplatin-, noise-, and age-induced hearing loss (Liu et al, 2021). Based on these findings, targeting autophagy to control mitochondrial quality appears to be a potential strategy to attenuate ototoxicity.…”

Section: Introductionmentioning

confidence: 99%

Mitophagy in ototoxicity

Han

Hu²,

Hu³

et al. 2023

Front. Cell. Neurosci.

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Mitochondrial dysfunction is associated with ototoxicity, which is caused by external factors. Mitophagy plays a key role in maintaining mitochondrial homeostasis and function and is regulated by a series of key mitophagy regulatory proteins and signaling pathways. The results of ototoxicity models indicate the importance of this process in the etiology of ototoxicity. A number of recent investigations of the control of cell fate by mitophagy have enhanced our understanding of the mechanisms by which mitophagy regulates ototoxicity and other hearing-related diseases, providing opportunities for targeting mitochondria to treat ototoxicity.

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Autophagy: A Novel Horizon for Hair Cell Protection

Cited by 8 publications

References 148 publications

MSC-derived exosomes protect auditory hair cells from neomycin-induced damage via autophagy regulation

MSC-derived exosomes protect auditory hair cells from neomycin-induced damage via autophagy regulation

Cellular autophagy, the compelling roles in hearing function and dysfunction

Mitophagy in ototoxicity

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