PMID- 36287265 OWN - NLM STAT- MEDLINE DCOM- 20230214 LR - 20230214 IS - 1432-0878 (Electronic) IS - 0302-766X (Linking) VI - 391 IP - 1 DP - 2023 Jan TI - HMGB1 accumulation in cytoplasm mediates noise-induced cochlear damage. PG - 43-54 LID - 10.1007/s00441-022-03696-9 [doi] AB - Damage-associated molecular pattern molecules (DAMPs) play a critical role in mediating cochlear cell death, which leads to noise-induced hearing loss (NIHL). High-mobility group box 1 (HMGB1), a prototypical DAMP released from cells, has been extensively studied in the context of various diseases. However, whether extracellular HMGB1 contributes to cochlear pathogenesis in NIHL and the potential signals initiating HMGB1 release from cochlear cells are not well understood. Here, through the transfection of the adeno-associated virus with HMGB1-HA-tag, we first investigated early cytoplasmic accumulation of HMGB1 in cochlear hair cells after noise exposure. We found that the cochlear administration of HMGB1-neutralizing antibody immediately after noise exposure significantly alleviated hearing loss and outer hair cells (OHCs) death induced by noise exposure. In addition, activation of signal transducer and activators of transcription 1 (STAT1) and cellular hyperacetylation were verified as potential canonical initiators of HMGB1 cytoplasmic accumulation. These findings reveal the adverse effects of extracellular HMGB1 on the cochlea and the potential signaling events mediating HMGB1 release in hair cells, indicating multiple potential pharmacotherapeutic targets for NIHL. CI - (c) 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Xiao, Lili AU - Xiao L AD - Department of Otolaryngology-Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China. AD - Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai, 200233, China. AD - Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai, 200233, China. FAU - Zhang, Zhen AU - Zhang Z AD - Department of Otolaryngology-Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China. AD - Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai, 200233, China. AD - Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai, 200233, China. FAU - Liu, Jianju AU - Liu J AD - School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. FAU - Zheng, Zhong AU - Zheng Z AD - Department of Otolaryngology-Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China. AD - Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai, 200233, China. AD - Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai, 200233, China. FAU - Xiong, Yuanping AU - Xiong Y AD - Department of Otolaryngology Head and Neck Surgery, First Affiliated Hospital of Nanchang University, Nanchang, 330000, China. FAU - Li, Chunyan AU - Li C AD - Department of Otolaryngology-Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China. 7250012693@shsmu.edu.cn. AD - Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai, 200233, China. 7250012693@shsmu.edu.cn. AD - Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai, 200233, China. 7250012693@shsmu.edu.cn. FAU - Feng, Yanmei AU - Feng Y AUID- ORCID: 0000-0003-4180-6564 AD - Department of Otolaryngology-Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China. ymfeng@sjtu.edu.cn. AD - Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai, 200233, China. ymfeng@sjtu.edu.cn. AD - Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai, 200233, China. ymfeng@sjtu.edu.cn. FAU - Yin, Shankai AU - Yin S AD - Department of Otolaryngology-Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China. yinshankai@china.com. AD - Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai, 200233, China. yinshankai@china.com. AD - Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai, 200233, China. yinshankai@china.com. LA - eng GR - NSFC/International Cooperation and Exchange of the National Natural Science Foundation of China/ GR - 81720108010/International Cooperation and Exchange of the National Natural Science Foundation of China/ GR - Nos. 8217040589/National Natural Science Foundation of China/ GR - Grant No. 18DZ2260200/Grants-in-Aid from Shanghai Municipal Commission of Science and Technology/ PT - Journal Article DEP - 20221026 PL - Germany TA - Cell Tissue Res JT - Cell and tissue research JID - 0417625 RN - 0 (HMGB1 Protein) SB - IM MH - Animals MH - Mice MH - *Cochlea/metabolism/pathology MH - Cytoplasm/metabolism MH - Hair Cells, Auditory, Outer/metabolism MH - *Hearing Loss, Noise-Induced/etiology/metabolism/pathology MH - *HMGB1 Protein/metabolism MH - *Noise/adverse effects OTO - NOTNLM OT - Cytosol accumulation OT - HMGB1 OT - Hearing loss OT - Noise exposure OT - STAT1 EDAT- 2022/10/27 06:00 MHDA- 2023/01/18 06:00 CRDT- 2022/10/26 11:15 PHST- 2022/03/11 00:00 [received] PHST- 2022/10/05 00:00 [accepted] PHST- 2022/10/27 06:00 [pubmed] PHST- 2023/01/18 06:00 [medline] PHST- 2022/10/26 11:15 [entrez] AID - 10.1007/s00441-022-03696-9 [pii] AID - 10.1007/s00441-022-03696-9 [doi] PST - ppublish SO - Cell Tissue Res. 2023 Jan;391(1):43-54. doi: 10.1007/s00441-022-03696-9. Epub 2022 Oct 26.