title: Transforming growth factor β1 inhibition protects from noise-induced hearing loss.
abstract: 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 β (TGF-β) 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-β as a therapeutic strategy for preventing or ameliorating noise-induced hearing loss (NIHL), we studied the auditory function, cochlear morphology, gene expression and oxidative stress markers in mice exposed to noise and treated with TGF-β1 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-β1 inhibitors were administered prior to inducing the injury. In conclusion, inhibition of TGF-β1 actions with antagonistic peptides represents a new, promising therapeutic strategy for the prevention and repair of noise-induced cochlear damage.
authors: Institute for Biomedical Research "Alberto Sols" (IIBM), Spanish National Research Council-Autonomous University of Madrid (CSIC-UAM) Madrid, Spain ; Centre for Biomedical Network Research (CIBER), Institute of Health Carlos III (ISCIII) Madrid, Spain ; Hospital La Paz Institute for Health Research (IdiPAZ) Madrid, Spain.
authors: Silvia
authors: S
authors: Murillo-Cuesta
authors: Institute for Biomedical Research "Alberto Sols" (IIBM), Spanish National Research Council-Autonomous University of Madrid (CSIC-UAM) Madrid, Spain ; Centre for Biomedical Network Research (CIBER), Institute of Health Carlos III (ISCIII) Madrid, Spain ; Hospital La Paz Institute for Health Research (IdiPAZ) Madrid, Spain.
authors: Lourdes
authors: L
authors: Rodríguez-de la Rosa
authors: Institute for Biomedical Research "Alberto Sols" (IIBM), Spanish National Research Council-Autonomous University of Madrid (CSIC-UAM) Madrid, Spain ; Centre for Biomedical Network Research (CIBER), Institute of Health Carlos III (ISCIII) Madrid, Spain ; Veterinary Faculty, Complutense University of Madrid Madrid, Spain.
authors: Julio
authors: J
authors: Contreras
authors: Institute for Biomedical Research "Alberto Sols" (IIBM), Spanish National Research Council-Autonomous University of Madrid (CSIC-UAM) Madrid, Spain ; Centre for Biomedical Network Research (CIBER), Institute of Health Carlos III (ISCIII) Madrid, Spain.
authors: Adelaida M
authors: AM
authors: Celaya
authors: Institute for Biomedical Research "Alberto Sols" (IIBM), Spanish National Research Council-Autonomous University of Madrid (CSIC-UAM) Madrid, Spain ; Centre for Biomedical Network Research (CIBER), Institute of Health Carlos III (ISCIII) Madrid, Spain ; Hospital La Paz Institute for Health Research (IdiPAZ) Madrid, Spain.
authors: Guadalupe
authors: G
authors: Camarero
authors: Institute for Biomedical Research "Alberto Sols" (IIBM), Spanish National Research Council-Autonomous University of Madrid (CSIC-UAM) Madrid, Spain ; Centre for Biomedical Network Research (CIBER), Institute of Health Carlos III (ISCIII) Madrid, Spain ; Príncipe de Asturias University Hospital, University of Alcalá, Alcalá de Henares Madrid, Spain.
authors: Teresa
authors: T
authors: Rivera
authors: Institute for Biomedical Research "Alberto Sols" (IIBM), Spanish National Research Council-Autonomous University of Madrid (CSIC-UAM) Madrid, Spain ; Centre for Biomedical Network Research (CIBER), Institute of Health Carlos III (ISCIII) Madrid, Spain ; Hospital La Paz Institute for Health Research (IdiPAZ) Madrid, Spain.
authors: Isabel
authors: I
authors: Varela-Nieto
keywords: TGF-β; cochlear injury; inflammation; noise-induced hearing loss; protection