Transforming growth factor β1 inhibition protects from noise-induced hearing loss
Excessive exposure to noise damages the principal cochlear structures leading to hearing impairment. Inflammatory and immune responses are central mechanisms in cochlear defensive response to noise but, if unregulated, they contribute to inner ear damage and hearing loss. Transforming growth factor...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2015-03-01
|
| Series: | Frontiers in Aging Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnagi.2015.00032/full |
| _version_ | 1828515655785119744 |
|---|---|
| author | Silvia eMurillo-Cuesta Silvia eMurillo-Cuesta Silvia eMurillo-Cuesta Lourdes eRodríguez-de La Rosa Lourdes eRodríguez-de La Rosa Lourdes eRodríguez-de La Rosa Julio eContreras Julio eContreras Julio eContreras Adelaida M Celaya Adelaida M Celaya Guadalupe eCamarero Guadalupe eCamarero Guadalupe eCamarero Teresa eRivera Teresa eRivera Teresa eRivera Isabel eVarela-Nieto Isabel eVarela-Nieto Isabel eVarela-Nieto |
| author_facet | Silvia eMurillo-Cuesta Silvia eMurillo-Cuesta Silvia eMurillo-Cuesta Lourdes eRodríguez-de La Rosa Lourdes eRodríguez-de La Rosa Lourdes eRodríguez-de La Rosa Julio eContreras Julio eContreras Julio eContreras Adelaida M Celaya Adelaida M Celaya Guadalupe eCamarero Guadalupe eCamarero Guadalupe eCamarero Teresa eRivera Teresa eRivera Teresa eRivera Isabel eVarela-Nieto Isabel eVarela-Nieto Isabel eVarela-Nieto |
| author_sort | Silvia eMurillo-Cuesta |
| collection | DOAJ |
| description | Excessive exposure to noise damages the principal cochlear structures leading to hearing impairment. Inflammatory and immune responses are central mechanisms in cochlear defensive response to noise but, if unregulated, they contribute to inner ear damage and hearing loss. Transforming growth factor ß (TGF-ß) is a key regulator of both responses and high levels of this factor have been associated with cochlear injury in hearing loss animal models. To evaluate the potential of targeting TGF-ß as a therapeutic strategy for preventing or ameliorating noise-induced hearing loss, we studied the auditory function, cochlear morphology, gene expression and oxidative stress markers in mice exposed to noise and treated with TGF-ß1 peptidic inhibitors P17 and P144, just before or immediately after noise insult. Our results indicate that systemic administration of both peptides significantly improved both the evolution of hearing thresholds and the degenerative changes induced by noise-exposure in lateral wall structures. Moreover, treatments ameliorated the inflammatory state and redox balance. These therapeutic effects were dose-dependent and more effective if the TGF-ß1 inhibitors were administered prior to inducing the injury. In conclusion, inhibition of TGF-ß1 actions with antagonistic peptides represents a new, promising therapeutic strategy for the prevention and repair of noise-induced cochlear damage. |
| first_indexed | 2024-12-11T18:16:59Z |
| format | Article |
| id | doaj.art-3171227a68194ddb8b8df6e3d9128905 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-11T18:16:59Z |
| publishDate | 2015-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-3171227a68194ddb8b8df6e3d91289052022-12-22T00:55:24ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652015-03-01710.3389/fnagi.2015.00032130219Transforming growth factor β1 inhibition protects from noise-induced hearing lossSilvia eMurillo-Cuesta0Silvia eMurillo-Cuesta1Silvia eMurillo-Cuesta2Lourdes eRodríguez-de La Rosa3Lourdes eRodríguez-de La Rosa4Lourdes eRodríguez-de La Rosa5Julio eContreras6Julio eContreras7Julio eContreras8Adelaida M Celaya9Adelaida M Celaya10Guadalupe eCamarero11Guadalupe eCamarero12Guadalupe eCamarero13Teresa eRivera14Teresa eRivera15Teresa eRivera16Isabel eVarela-Nieto17Isabel eVarela-Nieto18Isabel eVarela-Nieto19Institute for Biomedical Research “Alberto Sols” (IIBM), Spanish National Research Council–Autonomous University of Madrid (CSIC-UAM)Centre for Biomedical Network Research (CIBER), Institute of Health Carlos III (ISCIII)IdiPAZ Institute for Health ResearchInstitute for Biomedical Research “Alberto Sols” (IIBM), Spanish National Research Council–Autonomous University of Madrid (CSIC-UAM)Centre for Biomedical Network Research (CIBER), Institute of Health Carlos III (ISCIII)IdiPAZ Institute for Health ResearchVeterinary Faculty, Complutense University of MadridInstitute for Biomedical Research “Alberto Sols” (IIBM), Spanish National Research Council–Autonomous University of Madrid (CSIC-UAM)Centre for Biomedical Network Research (CIBER), Institute of Health Carlos III (ISCIII)Institute for Biomedical Research “Alberto Sols” (IIBM), Spanish National Research Council–Autonomous University of Madrid (CSIC-UAM)Centre for Biomedical Network Research (CIBER), Institute of Health Carlos III (ISCIII)Institute for Biomedical Research “Alberto Sols” (IIBM), Spanish National Research Council–Autonomous University of Madrid (CSIC-UAM)Centre for Biomedical Network Research (CIBER), Institute of Health Carlos III (ISCIII)IdiPAZ Institute for Health ResearchCentre for Biomedical Network Research (CIBER), Institute of Health Carlos III (ISCIII)Institute for Biomedical Research “Alberto Sols” (IIBM), Spanish National Research Council–Autonomous University of Madrid (CSIC-UAM)Príncipe de Asturias University Hospital, University of AlcaláInstitute for Biomedical Research “Alberto Sols” (IIBM), Spanish National Research Council–Autonomous University of Madrid (CSIC-UAM)Centre for Biomedical Network Research (CIBER), Institute of Health Carlos III (ISCIII)IdiPAZ Institute for Health ResearchExcessive exposure to noise damages the principal cochlear structures leading to hearing impairment. Inflammatory and immune responses are central mechanisms in cochlear defensive response to noise but, if unregulated, they contribute to inner ear damage and hearing loss. Transforming growth factor ß (TGF-ß) is a key regulator of both responses and high levels of this factor have been associated with cochlear injury in hearing loss animal models. To evaluate the potential of targeting TGF-ß as a therapeutic strategy for preventing or ameliorating noise-induced hearing loss, we studied the auditory function, cochlear morphology, gene expression and oxidative stress markers in mice exposed to noise and treated with TGF-ß1 peptidic inhibitors P17 and P144, just before or immediately after noise insult. Our results indicate that systemic administration of both peptides significantly improved both the evolution of hearing thresholds and the degenerative changes induced by noise-exposure in lateral wall structures. Moreover, treatments ameliorated the inflammatory state and redox balance. These therapeutic effects were dose-dependent and more effective if the TGF-ß1 inhibitors were administered prior to inducing the injury. In conclusion, inhibition of TGF-ß1 actions with antagonistic peptides represents a new, promising therapeutic strategy for the prevention and repair of noise-induced cochlear damage.http://journal.frontiersin.org/Journal/10.3389/fnagi.2015.00032/fullInflammationprotectionnoise-induced hearing lossTGF-ßcochlear injury |
| spellingShingle | Silvia eMurillo-Cuesta Silvia eMurillo-Cuesta Silvia eMurillo-Cuesta Lourdes eRodríguez-de La Rosa Lourdes eRodríguez-de La Rosa Lourdes eRodríguez-de La Rosa Julio eContreras Julio eContreras Julio eContreras Adelaida M Celaya Adelaida M Celaya Guadalupe eCamarero Guadalupe eCamarero Guadalupe eCamarero Teresa eRivera Teresa eRivera Teresa eRivera Isabel eVarela-Nieto Isabel eVarela-Nieto Isabel eVarela-Nieto Transforming growth factor β1 inhibition protects from noise-induced hearing loss Frontiers in Aging Neuroscience Inflammation protection noise-induced hearing loss TGF-ß cochlear injury |
| title | Transforming growth factor β1 inhibition protects from noise-induced hearing loss |
| title_full | Transforming growth factor β1 inhibition protects from noise-induced hearing loss |
| title_fullStr | Transforming growth factor β1 inhibition protects from noise-induced hearing loss |
| title_full_unstemmed | Transforming growth factor β1 inhibition protects from noise-induced hearing loss |
| title_short | Transforming growth factor β1 inhibition protects from noise-induced hearing loss |
| title_sort | transforming growth factor β1 inhibition protects from noise induced hearing loss |
| topic | Inflammation protection noise-induced hearing loss TGF-ß cochlear injury |
| url | http://journal.frontiersin.org/Journal/10.3389/fnagi.2015.00032/full |
| work_keys_str_mv | AT silviaemurillocuesta transforminggrowthfactorb1inhibitionprotectsfromnoiseinducedhearingloss AT silviaemurillocuesta transforminggrowthfactorb1inhibitionprotectsfromnoiseinducedhearingloss AT silviaemurillocuesta transforminggrowthfactorb1inhibitionprotectsfromnoiseinducedhearingloss AT lourdeserodriguezdelarosa transforminggrowthfactorb1inhibitionprotectsfromnoiseinducedhearingloss AT lourdeserodriguezdelarosa transforminggrowthfactorb1inhibitionprotectsfromnoiseinducedhearingloss AT lourdeserodriguezdelarosa transforminggrowthfactorb1inhibitionprotectsfromnoiseinducedhearingloss AT julioecontreras transforminggrowthfactorb1inhibitionprotectsfromnoiseinducedhearingloss AT julioecontreras transforminggrowthfactorb1inhibitionprotectsfromnoiseinducedhearingloss AT julioecontreras transforminggrowthfactorb1inhibitionprotectsfromnoiseinducedhearingloss AT adelaidamcelaya transforminggrowthfactorb1inhibitionprotectsfromnoiseinducedhearingloss AT adelaidamcelaya transforminggrowthfactorb1inhibitionprotectsfromnoiseinducedhearingloss AT guadalupeecamarero transforminggrowthfactorb1inhibitionprotectsfromnoiseinducedhearingloss AT guadalupeecamarero transforminggrowthfactorb1inhibitionprotectsfromnoiseinducedhearingloss AT guadalupeecamarero transforminggrowthfactorb1inhibitionprotectsfromnoiseinducedhearingloss AT teresaerivera transforminggrowthfactorb1inhibitionprotectsfromnoiseinducedhearingloss AT teresaerivera transforminggrowthfactorb1inhibitionprotectsfromnoiseinducedhearingloss AT teresaerivera transforminggrowthfactorb1inhibitionprotectsfromnoiseinducedhearingloss AT isabelevarelanieto transforminggrowthfactorb1inhibitionprotectsfromnoiseinducedhearingloss AT isabelevarelanieto transforminggrowthfactorb1inhibitionprotectsfromnoiseinducedhearingloss AT isabelevarelanieto transforminggrowthfactorb1inhibitionprotectsfromnoiseinducedhearingloss |