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Cisplatin-Induced Stria Vascularis Damage Is Associated with Inflammation and Fibrosis
The stria vascularis (SV) generates the endocochlear potential (EP) in the inner ear and is necessary for proper hair cell (HC) mechanotransduction and hearing. Cell junctions are indispensable for the establishment of compositionally distinct fluid compartments in the inner ear. Ototoxic drug cispl...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527906/ https://www.ncbi.nlm.nih.gov/pubmed/33029120 http://dx.doi.org/10.1155/2020/8851525 |
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author | Zhang, Na Cai, Jing Xu, Lei Wang, Haibo Liu, Wenwen |
author_facet | Zhang, Na Cai, Jing Xu, Lei Wang, Haibo Liu, Wenwen |
author_sort | Zhang, Na |
collection | PubMed |
description | The stria vascularis (SV) generates the endocochlear potential (EP) in the inner ear and is necessary for proper hair cell (HC) mechanotransduction and hearing. Cell junctions are indispensable for the establishment of compositionally distinct fluid compartments in the inner ear. Ototoxic drug cisplatin can damage SV and cause sensorineural hearing loss; however, the underlying mechanisms behind such injury are unclear. In this study, after the intraperitoneal injection of cisplatin (3 mg/kg/day for 7 days) in mice, we determined the auditory function by EP recording and auditory brainstem response (ABR) analysis, observed the ultrastructure of SV by transmission electron microscopy (TEM), and examined the expression and distribution of cell junction proteins by western blot, PCR, and immunofluorescence staining. We discovered that the EP was significantly reduced while ABR thresholds were significantly elevated in cisplatin-treated mice; cisplatin induced ultrastructural changes in marginal cells (MCs), endothelial cells (ECs), pericytes, etc. We found that cisplatin insulted auditory function not only by reducing the expression of zonula occludens protein-1 (ZO-1) in MCs of the SV but also by decreasing the expression of connexin 26 (Cx26) and connexin 43 (Cx43) in MCs and basal cells (BCs). More importantly, cisplatin induced activations of perivascular-resident macrophage-like melanocytes (PVM/Ms) and interleukin-1beta (IL-1β) as well as increased expressions of profibrotic proteins such as laminin and collagen IV in SV. Thus, our results firstly showed that cisplatin induced fibrosis, inflammation, and the complex expression change of cell junctions in SV. |
format | Online Article Text |
id | pubmed-7527906 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-75279062020-10-06 Cisplatin-Induced Stria Vascularis Damage Is Associated with Inflammation and Fibrosis Zhang, Na Cai, Jing Xu, Lei Wang, Haibo Liu, Wenwen Neural Plast Research Article The stria vascularis (SV) generates the endocochlear potential (EP) in the inner ear and is necessary for proper hair cell (HC) mechanotransduction and hearing. Cell junctions are indispensable for the establishment of compositionally distinct fluid compartments in the inner ear. Ototoxic drug cisplatin can damage SV and cause sensorineural hearing loss; however, the underlying mechanisms behind such injury are unclear. In this study, after the intraperitoneal injection of cisplatin (3 mg/kg/day for 7 days) in mice, we determined the auditory function by EP recording and auditory brainstem response (ABR) analysis, observed the ultrastructure of SV by transmission electron microscopy (TEM), and examined the expression and distribution of cell junction proteins by western blot, PCR, and immunofluorescence staining. We discovered that the EP was significantly reduced while ABR thresholds were significantly elevated in cisplatin-treated mice; cisplatin induced ultrastructural changes in marginal cells (MCs), endothelial cells (ECs), pericytes, etc. We found that cisplatin insulted auditory function not only by reducing the expression of zonula occludens protein-1 (ZO-1) in MCs of the SV but also by decreasing the expression of connexin 26 (Cx26) and connexin 43 (Cx43) in MCs and basal cells (BCs). More importantly, cisplatin induced activations of perivascular-resident macrophage-like melanocytes (PVM/Ms) and interleukin-1beta (IL-1β) as well as increased expressions of profibrotic proteins such as laminin and collagen IV in SV. Thus, our results firstly showed that cisplatin induced fibrosis, inflammation, and the complex expression change of cell junctions in SV. Hindawi 2020-09-22 /pmc/articles/PMC7527906/ /pubmed/33029120 http://dx.doi.org/10.1155/2020/8851525 Text en Copyright © 2020 Na Zhang et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Zhang, Na Cai, Jing Xu, Lei Wang, Haibo Liu, Wenwen Cisplatin-Induced Stria Vascularis Damage Is Associated with Inflammation and Fibrosis |
title | Cisplatin-Induced Stria Vascularis Damage Is Associated with Inflammation and Fibrosis |
title_full | Cisplatin-Induced Stria Vascularis Damage Is Associated with Inflammation and Fibrosis |
title_fullStr | Cisplatin-Induced Stria Vascularis Damage Is Associated with Inflammation and Fibrosis |
title_full_unstemmed | Cisplatin-Induced Stria Vascularis Damage Is Associated with Inflammation and Fibrosis |
title_short | Cisplatin-Induced Stria Vascularis Damage Is Associated with Inflammation and Fibrosis |
title_sort | cisplatin-induced stria vascularis damage is associated with inflammation and fibrosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527906/ https://www.ncbi.nlm.nih.gov/pubmed/33029120 http://dx.doi.org/10.1155/2020/8851525 |
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