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HMGB1 accumulation in cytoplasm mediates noise-induced cochlear damage

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Abstract

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.

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Funding

This research was supported by the International Cooperation and Exchange of the National Natural Science Foundation of China (NSFC; 81720108010), National Natural Science Foundation of China (Nos. 8217040589), and Grants-in-Aid from Shanghai Municipal Commission of Science and Technology (Grant No. 18DZ2260200).

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Author notes

  1. Lili Xiao and Zhen Zhang contributed equally to this work.

Authors and Affiliations

  1. Department of Otolaryngology–Head and Neck Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China

    Lili Xiao, Zhen Zhang, Zhong Zheng, Chunyan Li, Yanmei Feng & Shankai Yin

  2. Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai, 200233, China

    Lili Xiao, Zhen Zhang, Zhong Zheng, Chunyan Li, Yanmei Feng & Shankai Yin

  3. Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai, 200233, China

    Lili Xiao, Zhen Zhang, Zhong Zheng, Chunyan Li, Yanmei Feng & Shankai Yin

  4. School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

    Jianju Liu

  5. Department of Otolaryngology Head and Neck Surgery, First Affiliated Hospital of Nanchang University, Nanchang, 330000, China

    Yuanping Xiong

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  1. Lili Xiao
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Contributions

Conceptualization, C.L., Y.F., and S.Y.; methodology, L.X., Z.Z., J.L., Z.Z., Y.X., and C.L.; software, J.L., Z.Z., and Y.X.; data curation, L.X., Z.Z., J.L., Z.Z., and Y.X.; original draft preparation, L.X.; review and editing, Z.Z., C.L., Y.F., and S.Y.; funding acquisition, Y.F. and S.Y. All authors have read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to Chunyan Li, Yanmei Feng or Shankai Yin.

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The animal study was reviewed and approved by Institutional Animal Care and Use Committee (IACUC) of the Affiliated Sixth People’s Hospital, Shanghai Jiao Tong University School of Medicine (permit number DWLL2019-0179).

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Xiao, L., Zhang, Z., Liu, J. et al. HMGB1 accumulation in cytoplasm mediates noise-induced cochlear damage. Cell Tissue Res 391, 43–54 (2023). https://doi.org/10.1007/s00441-022-03696-9

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