{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T19:29:05Z","timestamp":1771874945902,"version":"3.50.1"},"reference-count":63,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T00:00:00Z","timestamp":1744588800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["22106034"],"award-info":[{"award-number":["22106034"]}]},{"name":"National Natural Science Foundation of China","award":["LY18H260002"],"award-info":[{"award-number":["LY18H260002"]}]},{"name":"Zhejiang Provincial Natural Science Foundation of China","award":["22106034"],"award-info":[{"award-number":["22106034"]}]},{"name":"Zhejiang Provincial Natural Science Foundation of China","award":["LY18H260002"],"award-info":[{"award-number":["LY18H260002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Age-related hearing loss (ARHL) is a highly prevalent, burdensome sensorineural hearing loss closely associated with impaired autophagic influx. Our previous studies revealed that neuritin, a neurotrophic factor primarily expressed in the central nervous system, could alleviate drug-induced damages in hair cells (HCs) and spiral ganglion neurons. However, its effects on ARHL and whether these effects are closely related to autophagy remain unclear. Using the Nrn1 knock-in mice and cultured cochlear basilar membrane (CBM) of the neonatal mouse, we show that neuritin could restore aging-associated hearing loss and alleviate senescence-associated damage in the cochlea. Overexpression of neuritin in support cells (SCs) alleviates the loss of cochlear HCs and nerve fibers, reducing the damage to spiral ganglion neurons and the shifts in ABR\u2019s high-frequency threshold. Furthermore, conditional overexpression of neuritin in SCs improves autophagic influx by upregulating the expression of microtubule-associated protein 1 light chain 3 type B (LCB3) protein and downregulating the expression of p21 protein. In cultured neonatal mouse CBM, neuritin administration significantly inhibits D-galactose-induced HC loss, cellular apoptosis, and ROS production and promotes autophagic influx. These effects were weakened when the autophagy inhibitor 3-MA was added. In summary, our results confirm the therapeutic potential of neuritin treatment for ARHL.<\/jats:p>","DOI":"10.3390\/ijms26083709","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T03:59:06Z","timestamp":1744689546000},"page":"3709","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Conditional Overexpression of Neuritin in Supporting Cell Protects Cochlear Hair Cell and Delays Age-Related Hearing Loss by Enhancing Autophagy"],"prefix":"10.3390","volume":"26","author":[{"given":"Shanshan","family":"Wang","sequence":"first","affiliation":[{"name":"School of Public Health, Hangzhou Normal University, Hangzhou 311121, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0244-2830","authenticated-orcid":false,"given":"Shaowei","family":"Lv","sequence":"additional","affiliation":[{"name":"School of Public Health, Hangzhou Normal University, Hangzhou 311121, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junhao","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Public Health, Hangzhou Normal University, Hangzhou 311121, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunfan","family":"Shi","sequence":"additional","affiliation":[{"name":"School of Public Health, Hangzhou Normal University, Hangzhou 311121, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Li","sequence":"additional","affiliation":[{"name":"School of Public Health, Hangzhou Normal University, Hangzhou 311121, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianyun","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Public Health, Hangzhou Normal University, Hangzhou 311121, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3864-5301","authenticated-orcid":false,"given":"Xiaohua","family":"Tan","sequence":"additional","affiliation":[{"name":"School of Public Health, Hangzhou Normal University, Hangzhou 311121, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Public Health, Hangzhou Normal University, Hangzhou 311121, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Hong","sequence":"additional","affiliation":[{"name":"School of Public Health, Hangzhou Normal University, Hangzhou 311121, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1056\/NEJMcp2306778","article-title":"Age-Related Hearing Loss","volume":"390","author":"Lin","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1056\/NEJMra1616601","article-title":"Hearing Loss in Adults","volume":"377","author":"Cunningham","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"110665","DOI":"10.1016\/j.celrep.2022.110665","article-title":"Molecular and Cytological Profiling of Biological Aging of Mouse Cochlear Inner and Outer Hair Cells","volume":"39","author":"Liu","year":"2022","journal-title":"Cell Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"12587","DOI":"10.18632\/aging.202936","article-title":"Neural Presbycusis at Ultra-High Frequency in Aged Common Marmosets and Rhesus Monkeys","volume":"13","author":"Sun","year":"2021","journal-title":"Aging"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"25944","DOI":"10.18632\/aging.203782","article-title":"Global, Regional, and National Burden of Age-Related Hearing Loss from 1990 to 2019","volume":"13","author":"Man","year":"2021","journal-title":"Aging"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/S0140-6736(21)00522-5","article-title":"Addressing the Global Burden of Hearing Loss","volume":"397","author":"Wilson","year":"2021","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1001\/jamaoto.2018.2875","article-title":"Trends in Health Care Costs and Utilization Associated with Untreated Hearing Loss over 10 Years","volume":"145","author":"Reed","year":"2019","journal-title":"JAMA Otolaryngol. Head Neck Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1001\/jamaoto.2017.2513","article-title":"Association of Age-Related Hearing Loss with Cognitive Function, Cognitive Impairment, and Dementia: A Systematic Review and Meta-Analysis","volume":"144","author":"Loughrey","year":"2018","journal-title":"JAMA Otolaryngol. Head Neck Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/s43587-024-00606-2","article-title":"Hearing loss promotes Alzheimer\u2019s disease","volume":"4","author":"Zhao","year":"2024","journal-title":"Nat Aging"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1001\/archinternmed.2011.728","article-title":"Hearing Loss and Falls among Older Adults in the United States","volume":"172","author":"Lin","year":"2012","journal-title":"Arch. Intern. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1093\/ageing\/aft122","article-title":"Impairments in Hearing and Vision Impact on Mortality in Older People: The Ages-Reykjavik Study","volume":"43","author":"Fisher","year":"2014","journal-title":"Age Ageing"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1097\/MAO.0000000000002194","article-title":"Hearing Protection, Restoration, and Regeneration: An Overview of Emerging Therapeutics for Inner Ear and Central Hearing Disorders","volume":"40","author":"Schilder","year":"2019","journal-title":"Otol. Neurotol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Yang, W., Zhao, X.L., Chai, R.J., and Fan, J.A. (2023). Progress on Mechanisms of Age-Related Hearing Loss. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1253574"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e3079","DOI":"10.1038\/cddis.2017.462","article-title":"Activation of Mir-34a Impairs Autophagic Flux and Promotes Cochlear Cell Death Via Repressing: Implications for Age-Related Hearing Loss","volume":"8","author":"Pang","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"108783","DOI":"10.1016\/j.heares.2023.108783","article-title":"Role of Mitochondrial Dysfunction and Oxidative Stress in Sensorineural Hearing Loss","volume":"434","author":"Tan","year":"2023","journal-title":"Hear. Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Park, D.J., Ha, S., Choi, J.S., Lee, S.H., Park, J.E., and Seo, Y.J. (2020). Induced Short-Term Hearing Loss Due to Stimulation of Age-Related Factors by Intermittent Hypoxia, High-Fat Diet, and Galactose Injection. Int. J. Mol. Sci., 21.","DOI":"10.20944\/preprints202007.0505.v1"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e14091","DOI":"10.1111\/acel.14091","article-title":"Excessive Processing and Acetylation of Opa1 Aggravate Age-Related Hearing Loss Via the Dysregulation of Mitochondrial Dynamics","volume":"23","author":"Zhang","year":"2024","journal-title":"Aging Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e13909","DOI":"10.1111\/acel.13909","article-title":"Long-Term Nad Plus Supplementation Prevents the Progression of Age-Related Hearing Loss in Mice","volume":"22","author":"Okur","year":"2023","journal-title":"Aging Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"137897","DOI":"10.1016\/j.neulet.2024.137897","article-title":"Vitamin C Inhibits Nlrp3 Inflammasome Activation and Delays the Development of Age-Related Hearing Loss in Male C57bl\/6 Mice","volume":"836","author":"Liu","year":"2024","journal-title":"Neurosci. Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"108689","DOI":"10.1016\/j.heares.2023.108689","article-title":"Current Development of Patient-Specific Induced Pluripotent Stem Cells Harbouring Mitochondrial Gene Mutations and Their Applications in the Treatment of Sensorineural Hearing Loss","volume":"429","author":"Chou","year":"2023","journal-title":"Hear. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4341","DOI":"10.1080\/15548627.2021.1916194","article-title":"Foxg1 Promotes Aging Inner Ear Hair Cell Survival through Activation of the Autophagy Pathway","volume":"17","author":"He","year":"2021","journal-title":"Autophagy"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.neurobiolaging.2019.04.003","article-title":"Sirt1 Protects Cochlear Hair Cell and Delays Age-Related Hearing Loss Via Autophagy","volume":"80","author":"Pang","year":"2019","journal-title":"Neurobiol. Aging"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Salam, S.A., Mostafa, F., Alnamshan, M.M., Elshewemi, S.S., and Sorour, J.M. (2021). Thymoquinone Ameliorates Age-Related Hearing Loss in C57bl\/6j Mice by Modulating Sirt1 Activity and Bak1 Expression. Biomed. Pharmacother., 143.","DOI":"10.1016\/j.biopha.2021.112149"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.neurobiolaging.2019.03.013","article-title":"Modulation of Mir-34a\/Sirt1 Signaling Protects Cochlear Hair Cells against Oxidative Stress and Delays Age-Related Hearing Loss through Coordinated Regulation of Mitophagy and Mitochondrial Biogenesis","volume":"79","author":"Xiong","year":"2019","journal-title":"Neurobiol. Aging"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1017\/S0022215112003118","article-title":"Evaluation of Antioxidant Treatment in Presbyacusis: Prospective, Placebo-Controlled, Double-Blind, Randomised Trial","volume":"127","author":"Polanski","year":"2013","journal-title":"J. Laryngol. Otol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1159\/000493011","article-title":"Combined Growth Factor and Gene Therapy: An Approach for Hair Cell Regeneration and Hearing Recovery","volume":"80","author":"Jamshidi","year":"2018","journal-title":"ORL J. Otorhinolaryngol. Relat. Spec."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.2174\/0929867321666131218093327","article-title":"Neuritin, a Neurotrophic Factor in Nervous System Physiology","volume":"21","author":"Zhou","year":"2014","journal-title":"Curr. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Lu, J., Li, Z., Zhao, Q., Liu, D., and Mei, Y.A. (2021). Neuritin Improves the Neurological Functional Recovery after Experimental Intracerebral Hemorrhage in Mice. Neurobiol. Dis., 156.","DOI":"10.1016\/j.nbd.2021.105407"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1089\/hum.2015.159","article-title":"Exogenous Neuritin Promotes Nerve Regeneration after Acute Spinal Cord Injury in Rats","volume":"27","author":"Gao","year":"2016","journal-title":"Hum. Gene Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2681","DOI":"10.18632\/aging.202318","article-title":"Neuritin-Overexpressing Transgenic Mice Demonstrate Enhanced Neuroregeneration Capacity and Improved Spatial Learning and Memory Recovery after Ischemia-Reperfusion Injury","volume":"13","author":"Wan","year":"2020","journal-title":"Aging"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.neures.2023.11.001","article-title":"Exogenous Neuritin Restores Auditory Following Cochlear Spiral Ganglion Neuron Denervation of Gerbils","volume":"200","author":"Fei","year":"2024","journal-title":"Neurosci. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"108515","DOI":"10.1016\/j.heares.2022.108515","article-title":"Conditional Overexpression of Neuritin in Supporting Cells (Scs) Mitigates Hair Cell (Hc) Damage and Induces Hc Regeneration in the Adult Mouse Cochlea after Drug-Induced Ototoxicity","volume":"420","author":"Huang","year":"2022","journal-title":"Hear. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e12915","DOI":"10.1111\/cpr.12915","article-title":"Programmed Cell Death Pathways in Hearing Loss: A Review of Apoptosis, Autophagy and Programmed Necrosis","volume":"53","author":"Wu","year":"2020","journal-title":"Cell Prolif."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"148909","DOI":"10.1016\/j.brainres.2024.148909","article-title":"Neuritin Promotes Autophagic Flux by Inhibiting the Cgas-Sting Pathway to Alleviate Brain Injury after Subarachnoid Haemorrhage","volume":"1836","author":"Zhang","year":"2024","journal-title":"Brain Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"112832","DOI":"10.1016\/j.yexcr.2021.112832","article-title":"Neuritin Attenuates Oxygen-Glucose Deprivation\/Reoxygenation (Ogd\/R)-Induced Neuronal Injury by Promoting Autophagic Flux","volume":"407","author":"Zhang","year":"2021","journal-title":"Exp. Cell Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Zou, T., Xie, R., Huang, S., Lu, D., and Liu, J. (2024). Potential Role of Modulating Autophagy Levels in Sensorineural Hearing Loss. Biochem. Pharmacol., 222.","DOI":"10.1016\/j.bcp.2024.116115"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2648","DOI":"10.1073\/pnas.94.6.2648","article-title":"Neuritin: A Gene Induced by Neural Activity and Neurotrophins That Promotes Neuritogenesis","volume":"94","author":"Naeve","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/acel.13708","article-title":"Cochlear Neurotrophin-3 Overexpression at Mid-Life Prevents Age-Related Inner Hair Cell Synaptopathy and Slows Age-Related Hearing Loss","volume":"21","author":"Cassinotti","year":"2022","journal-title":"Aging Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.18632\/aging.101045","article-title":"Age-Related Hearing Loss: Prevention of Threshold Declines, Cell Loss and Apoptosis in Spiral Ganglion Neurons","volume":"8","author":"Frisina","year":"2016","journal-title":"Aging"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Wang, H., Li, X., Shan, L., Zhu, J., Chen, R., Li, Y., Yuan, W., Yang, L., and Huang, J. (2016). Recombinant Hneuritin Promotes Structural and Functional Recovery of Sciatic Nerve Injury in Rats. Front. Neurosci., 10.","DOI":"10.3389\/fnins.2016.00589"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1038\/aps.2017.197","article-title":"Functions and the Related Signaling Pathways of the Neurotrophic Factor Neuritin","volume":"39","author":"Yao","year":"2018","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1097\/01.moo.0000180919.68812.b9","article-title":"Strategies to Preserve or Regenerate Spiral Ganglion Neurons","volume":"13","author":"Roehm","year":"2005","journal-title":"Curr. Opin. Otolaryngol. Head Neck Surg."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Ji, L., Borges, B.C., Martel, D.T., Wu, C., Liberman, M.C., Shore, S.E., and Corfas, G. (2024). From Hidden Hearing Loss to Supranormal Auditory Processing by Neurotrophin 3-Mediated Modulation of Inner Hair Cell Synapse Density. PLoS Biol., 22.","DOI":"10.1371\/journal.pbio.3002665"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"108967","DOI":"10.1016\/j.heares.2024.108967","article-title":"Hidden Hearing Loss: Fifteen Years at a Glance","volume":"443","author":"Liu","year":"2024","journal-title":"Hear. Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Alberti, G., Portelli, D., and Galletti, C. (2023). Healthcare Professionals and Noise-Generating Tools: Challenging Assumptions About Hearing Loss Risk. Int. J. Environ. Res. Public Health, 20.","DOI":"10.3390\/ijerph20156520"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"10166","DOI":"10.1111\/jcmm.15627","article-title":"Exogenous Neuritin Treatment Improves Survivability and Functions of Schwann Cells with Improved Outgrowth of Neurons in Rat Diabetic Neuropathy","volume":"24","author":"Xi","year":"2020","journal-title":"J. Cell Mol. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"107391","DOI":"10.1016\/j.jstrokecerebrovasdis.2023.107391","article-title":"Neuritin Has a Neuroprotective Role in the Rat Model of Acute Ischemia Stroke by Inhibiting Neuronal Apoptosis and Nlrp3 Inflammasome","volume":"32","author":"Xu","year":"2023","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1038\/s41419-018-1229-y","article-title":"Dysregulated Autophagy Contributes to Caspase-Dependent Neuronal Apoptosis","volume":"9","author":"Chung","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1038\/cdd.2017.43","article-title":"Caspase Involvement in Autophagy","volume":"24","author":"Tsapras","year":"2017","journal-title":"Cell Death Differ."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Wan, H., Zhang, Y., and Hua, Q. (2022). Cellular Autophagy, the Compelling Roles in Hearing Function and Dysfunction. Front. Cell Neurosci., 16.","DOI":"10.3389\/fncel.2022.966202"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e70012","DOI":"10.1111\/jcmm.70012","article-title":"Neuritin Accelerates Schwann Cell Dedifferentiation Via Pi3k\/Akt\/Mtor Signalling Pathway During Wallerian Degeneration","volume":"28","author":"Liu","year":"2024","journal-title":"J. Cell. Mol. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"9980444","DOI":"10.1155\/2021\/9980444","article-title":"Pin1 Protects Hair Cells and Auditory Hei-Oc1 Cells against Senescence by Inhibiting the Pi3k\/Akt\/Mtor Pathway","volume":"2021","author":"Zhang","year":"2021","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2694","DOI":"10.1016\/j.cellsig.2014.08.019","article-title":"The Role of Pi3k\/Akt\/Mtor Pathway in the Modulation of Autophagy and the Clearance of Protein Aggregates in Neurodegeneration","volume":"26","year":"2014","journal-title":"Cell Signal"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"17369","DOI":"10.1074\/jbc.M115.708883","article-title":"Neuritin up-Regulates Kv4.2 Alpha-Subunit of Potassium Channel Expression and Affects Neuronal Excitability by Regulating the Calcium-Calcineurin-Nfatc4 Signaling Pathway","volume":"291","author":"Yao","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4082","DOI":"10.1016\/j.cell.2022.09.001","article-title":"Calcium Transients on the Er Surface Trigger Liquid-Liquid Phase Separation of Fip200 to Specify Autophagosome Initiation Sites","volume":"185","author":"Zheng","year":"2022","journal-title":"Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.heares.2016.11.013","article-title":"Cellular Mechanisms of Noise-Induced Hearing Loss","volume":"349","author":"Kurabi","year":"2017","journal-title":"Hear. Res."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Percie du Sert, N., Hurst, V., Ahluwalia, A., Alam, S., Avey, M.T., Baker, M., Browne, W.J., Clark, A., Cuthill, I.C., and Dirnagl, U. (2020). The Arrive Guidelines 2.0: Updated Guidelines for Reporting Animal Research. PLoS Biol., 18.","DOI":"10.1371\/journal.pbio.3000410"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1038\/nprot.2014.134","article-title":"Generating Genetically Modified Mice Using Crispr\/Cas-Mediated Genome Engineering","volume":"9","author":"Yang","year":"2014","journal-title":"Nat. Protoc."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Walters, B.J., Yamashita, T., and Zuo, J. (2015). Sox2-Creer Mice Are Useful for Fate Mapping of Mature, but Not Neonatal, Cochlear Supporting Cells in Hair Cell Regeneration Studies. Sci. Rep., 5.","DOI":"10.1038\/srep11621"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Guo, L., Lu, X., Cheng, C., Sun, S., Li, W., Zhao, L., Lai, C., Zhang, S., and Yu, C. (2018). Characterization of Lgr6+ Cells as an Enriched Population of Hair Cell Progenitors Compared to Lgr5+ Cells for Hair Cell Generation in the Neonatal Mouse Cochlea. Front. Mol. Neurosci., 11.","DOI":"10.3389\/fnmol.2018.00147"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"8167","DOI":"10.1073\/pnas.1202774109","article-title":"Wnt Signaling Induces Proliferation of Sensory Precursors in the Postnatal Mouse Cochlea","volume":"109","author":"Chai","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e1605","DOI":"10.1038\/cddis.2014.549","article-title":"Bmi1 Regulates Auditory Hair Cell Survival by Maintaining Redox Balance","volume":"6","author":"Chen","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"5950","DOI":"10.1007\/s12035-019-1493-6","article-title":"Ros-Induced Activation of DNA Damage Responses Drives Senescence-Like State in Postmitotic Cochlear Cells: Implication for Hearing Preservation","volume":"56","author":"Benkafadar","year":"2019","journal-title":"Mol. Neurobiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/8\/3709\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:14:28Z","timestamp":1760030068000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/8\/3709"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,14]]},"references-count":63,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["ijms26083709"],"URL":"https:\/\/doi.org\/10.3390\/ijms26083709","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,14]]}}}