The Role of Extracellular Vesicles in Diseases of the Ear, Nose, and Throat
Abstract
:1. Introduction
2. Biology of Extracellular Vesicles
2.1. EV Biogenesis
2.2. EV Cargo
2.3. EV Isolation
2.4. EV Characterization
3. Role of EVs in Diseases of the Ear, Nose, and Throat
3.1. Head and Neck Cancer
3.2. Otitis Media
3.3. Chronic Rhinosinusitis
3.4. Acquired Cholesteatoma
3.5. Ototoxicity
4. Summary and Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Reported Role of EVs | References |
---|---|
Metastasis and Proliferation:
| [37,40,42,43,44,45,46,47,48] |
Lymphocyte regulation:
| [50,51,53,54,55] |
Angiogenesis:
| [59,60,61,62,63,64,65] |
Microenvironment remodeling:
| [68,69,70,72,73,74,75] |
Drug resistance:
| [77,78,79] |
Disease | Reported Role of EVs | References |
---|---|---|
Otitis Media | Disease-related bacterial products drive differential expression of miRNAs within human middle ear epithelial cells (HMEECs). Exosomes collected from COM patients have a high abundance of miRNAs, most significantly miR-223-3p, miR-451a, miR-16a-2p, miR-320e, and miR-25-3p; and these miRNAs target genes that upregulate many IL-8-mediated cellular functions and CXCR1/2-mediated signaling. | [86,87] |
Chronic Rhinosinusitis | Significant differences in EV-cargo protein profiles were found between CRSwNP and control individuals, specifically molecular markers of CRSwNP including cystatin, glycoprotein VI, and peroxiredoxin-5. Elevated levels of epithelial protease inhibitors cystatin-1 and -2 are found in EVs isolated from nasal fluids of CRS patients. EVs from CRS patients potentially lead to the formation of polyps via their role in upregulating pappalysin and serpins. | [91,92,93] |
Acquired Cholesteatoma | Exosomal miR-17 of keratinocyte origin leads to the upregulation of fibroblast protein expression. | [98] |
Ototoxicity | In response to heat stress, cells of the inner ear release exosomes carrying Hsp70 which interacts with TLR4 on the hair cells, thereby providing a protective effect from aminoglycoside antibiotics. In mice treated with cisplatin, inner ear EVs are reduced in number and have significantly lower cargo protein concentration; proteomic analysis shows a significant increase in protein expression of Tmem 33, Pgm1, Eif3f, Rps24, Cct8, Hsd17b4, Aldh3a1, Ddost, Aldh3a1, Eif3c, Luc7l2, and Acadvl. Delivery of NPC-EVs transfected with miR-21 in vivo reduces caspase-3/parvalbumin expression, increases IL-10 expression, and prevents an increase in TNF-α and IL-1β expression of cochlear hair cells. Hypoxic BMSCs reduce cisplatin-induced ototoxicity by upregulating HIF-1α, superoxide dismutase 1 (SOD1), and SOD2 expression. Trans-tympanic delivery of HS-BMSC-Exos reverses cisplatin-induced upregulation of IL-1β, IL-6, TNF-α, NLRP3, ASC, cleaved caspase-1, and pro-caspase-1. Delivery of IEC-Exo-miR-182-5p to gentamicin-treated HEI-OC1 cells increases Bcl-2 expression and decreases FOXO3 and Bax expression. | [99,102,103,104,105,106] |
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Carnino, J.M.; Miyawaki, S.; Rampam, S. The Role of Extracellular Vesicles in Diseases of the Ear, Nose, and Throat. Med. Sci. 2023, 11, 6. https://doi.org/10.3390/medsci11010006
Carnino JM, Miyawaki S, Rampam S. The Role of Extracellular Vesicles in Diseases of the Ear, Nose, and Throat. Medical Sciences. 2023; 11(1):6. https://doi.org/10.3390/medsci11010006
Chicago/Turabian StyleCarnino, Jonathan M, Steven Miyawaki, and Sanjeev Rampam. 2023. "The Role of Extracellular Vesicles in Diseases of the Ear, Nose, and Throat" Medical Sciences 11, no. 1: 6. https://doi.org/10.3390/medsci11010006