Institute for Biomedical Research “Alberto Sols” (IIBM), Spanish National Research Council-Autonomous University of Madrid (CSIC-UAM), Madrid, Spain; Centre for Biomedical Network Research on Rare Diseases (CIBERER), CIBER, ISCIII, Madrid, Spain
Institute for Biomedical Research “Alberto Sols” (IIBM), Spanish National Research Council-Autonomous University of Madrid (CSIC-UAM), Madrid, Spain; Centre for Biomedical Network Research on Rare Diseases (CIBERER), CIBER, ISCIII, Madrid, Spain; Hospital La Paz Institute for Health Research (IdiPAZ), Madrid, Spain; Biochemistry Department, Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain; Biomedicine Unit UCLM-CSIC, Madrid, Spain
Institute for Biomedical Research “Alberto Sols” (IIBM), Spanish National Research Council-Autonomous University of Madrid (CSIC-UAM), Madrid, Spain; Centre for Biomedical Network Research on Rare Diseases (CIBERER), CIBER, ISCIII, Madrid, Spain
Lourdes Rodríguez-de la Rosa
Institute for Biomedical Research “Alberto Sols” (IIBM), Spanish National Research Council-Autonomous University of Madrid (CSIC-UAM), Madrid, Spain; Centre for Biomedical Network Research on Rare Diseases (CIBERER), CIBER, ISCIII, Madrid, Spain; Hospital La Paz Institute for Health Research (IdiPAZ), Madrid, Spain
Laura Pintado-Berninches
Institute for Biomedical Research “Alberto Sols” (IIBM), Spanish National Research Council-Autonomous University of Madrid (CSIC-UAM), Madrid, Spain; Hospital La Paz Institute for Health Research (IdiPAZ), Madrid, Spain
Rosario Perona
Institute for Biomedical Research “Alberto Sols” (IIBM), Spanish National Research Council-Autonomous University of Madrid (CSIC-UAM), Madrid, Spain; Centre for Biomedical Network Research on Rare Diseases (CIBERER), CIBER, ISCIII, Madrid, Spain; Hospital La Paz Institute for Health Research (IdiPAZ), Madrid, Spain
Institute for Biomedical Research “Alberto Sols” (IIBM), Spanish National Research Council-Autonomous University of Madrid (CSIC-UAM), Madrid, Spain; Centre for Biomedical Network Research on Rare Diseases (CIBERER), CIBER, ISCIII, Madrid, Spain
Institute for Biomedical Research “Alberto Sols” (IIBM), Spanish National Research Council-Autonomous University of Madrid (CSIC-UAM), Madrid, Spain; Centre for Biomedical Network Research on Rare Diseases (CIBERER), CIBER, ISCIII, Madrid, Spain
Mitogen-activated protein kinases (MAPK) such as p38 and the c-Jun N-terminal kinases (JNKs) are activated during the cellular response to stress signals. Their activity is regulated by the MAPK-phosphatase 1 (DUSP1), a key component of the anti-inflammatory response. Stress kinases are well-described elements of the response to otic injury and the otoprotective potential of JNK inhibitors is being tested in clinical trials. By contrast, there are no studies exploring the role of DUSP1 in hearing and hearing loss. Here we show that Dusp1 expression is age-regulated in the mouse cochlea. Dusp1 gene knock-out caused premature progressive hearing loss, as confirmed by auditory evoked responses in Dusp1–/– mice. Hearing loss correlated with cell death in hair cells, degeneration of spiral neurons and increased macrophage infiltration. Dusp1–/– mouse cochleae showed imbalanced redox status and dysregulated expression of cytokines. These data suggest that DUSP1 is essential for cochlear homeostasis in the response to stress during ageing.
