{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T18:46:37Z","timestamp":1782931597189,"version":"3.54.5"},"reference-count":49,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T00:00:00Z","timestamp":1740700800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T00:00:00Z","timestamp":1740700800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371153"],"award-info":[{"award-number":["82371153"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2021MH378;ZR2022QH073"],"award-info":[{"award-number":["ZR2021MH378;ZR2022QH073"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Inflammation plays an important role in age\u2010related hearing loss (ARHL). Transforming growth factor\u2010\u03b2\u2010activated protein 1 (TAK1), a key factor upstream of inflammatory pathways, mediates various cell death pathways, potentially influencing the survival and death of cochlear hair cells. The DBA\/2\u2009J mouse model and the HEI\u2010OC1 cell line were used to investigate the mechanism of TAK1\u2010mediated inflammation in ARHL. Hematoxylin and eosin staining revealed significant histological damage in the cochlea of 16\u2010week\u2010old mice, along with an increase in auditory\u2010evoked brainstem response thresholds. Concurrently, TAK1 mRNA levels decreased sharply, and necroptosis significantly increased in 16\u2010week\u2010old mice, indicating a correlation between TAK1 expression, necroptosis, and hearing loss. We subsequently constructed TAK1 knockdown and overexpression HEI\u2010OC1 cells for further investigation. TAK1 knockdown in HEI\u2010OC1 cells significantly activated the necroptotic pathway, characterized by an increase in necroptosis, along with up\u2010regulation of\n                    <jats:italic>RIPK3<\/jats:italic>\n                    and\n                    <jats:italic>MLKL<\/jats:italic>\n                    , and down\u2010regulation of\n                    <jats:italic>NF\u2010\u03baB<\/jats:italic>\n                    and\n                    <jats:italic>Caspase 8<\/jats:italic>\n                    . However, TAK1 overexpression successfully prevented necroptosis in HEI\u2010OC1 cells, leading to decreases in\n                    <jats:italic>NF\u2010\u03baB<\/jats:italic>\n                    ,\n                    <jats:italic>Caspase 8<\/jats:italic>\n                    ,\n                    <jats:italic>RIPK3<\/jats:italic>\n                    , and\n                    <jats:italic>MLKL<\/jats:italic>\n                    . We further treated TAK1 knockdown cells with necroptosis inhibitors and found that they could reverse the damage caused by TAK1 knockdown in HEI\u2010OC1 cells. This preliminary study shows that TAK1\u2010mediated necroptotic pathways play an important role in the pathogenesis of ARHL.\n                  <\/jats:p>","DOI":"10.1111\/acel.70013","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T07:03:14Z","timestamp":1741676594000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Transforming Growth Factor\u2010\u03b2\u2010Activated Protein 1 (\n                    <scp>TAK1<\/scp>\n                    ) Regulates Necroptosis in Age\u2010Related Hearing Loss"],"prefix":"10.1111","volume":"24","author":[{"given":"Hanjing","family":"Wang","sequence":"first","affiliation":[{"name":"School of Clinical Medicine Shandong Second Medical University  Weifang Shandong People's Republic of China"},{"name":"Department of Otorhinolaryngology, Head and Neck Surgery Yantai Yuhuangding Hospital, Qingdao University  Yantai Shandong People's Republic of China"},{"name":"Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation  Yantai Shandong People's Republic of China"},{"name":"Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases  Yantai Shandong People's Republic of China"},{"name":"Yantai Key Laboratory of Otorhinolaryngologic Diseases  Yantai Shandong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yayun","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery Yantai Yuhuangding Hospital, Qingdao University  Yantai Shandong People's Republic of China"},{"name":"Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation  Yantai Shandong People's Republic of China"},{"name":"Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases  Yantai Shandong People's Republic of China"},{"name":"Yantai Key Laboratory of Otorhinolaryngologic Diseases  Yantai Shandong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery Yantai Yuhuangding Hospital, Qingdao University  Yantai Shandong People's Republic of China"},{"name":"Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation  Yantai Shandong People's Republic of China"},{"name":"Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases  Yantai Shandong People's Republic of China"},{"name":"Yantai Key Laboratory of Otorhinolaryngologic Diseases  Yantai Shandong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihong","family":"Hao","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine Shandong Second Medical University  Weifang Shandong People's Republic of China"},{"name":"Department of Otorhinolaryngology, Head and Neck Surgery Yantai Yuhuangding Hospital, Qingdao University  Yantai Shandong People's Republic of China"},{"name":"Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation  Yantai Shandong People's Republic of China"},{"name":"Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases  Yantai Shandong People's Republic of China"},{"name":"Yantai Key Laboratory of Otorhinolaryngologic Diseases  Yantai Shandong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Zhai","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery Yantai Yuhuangding Hospital, Qingdao University  Yantai Shandong People's Republic of China"},{"name":"Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation  Yantai Shandong People's Republic of China"},{"name":"Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases  Yantai Shandong People's Republic of China"},{"name":"Yantai Key Laboratory of Otorhinolaryngologic Diseases  Yantai Shandong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery Yantai Yuhuangding Hospital, Qingdao University  Yantai Shandong People's Republic of China"},{"name":"Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation  Yantai Shandong People's Republic of China"},{"name":"Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases  Yantai Shandong People's Republic of China"},{"name":"Yantai Key Laboratory of Otorhinolaryngologic Diseases  Yantai Shandong People's Republic of China"},{"name":"The Second School of Clinical Medicine of Binzhou Medical University  Yantai Shandong People's Republic of 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Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70013","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.70013","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70013","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T23:09:43Z","timestamp":1781132983000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.70013"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,28]]},"references-count":49,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1111\/acel.70013"],"URL":"https:\/\/doi.org\/10.1111\/acel.70013","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,28]]},"assertion":[{"value":"2024-10-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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