Xiao Lili, Sun Yan, Liu Chengqi, Zheng Zhong, Shen Ying, Xia Liang, Yang Guang, Feng Yanmei
Department of Otolaryngology-Head and Neck Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai, China.
Front Cell Dev Biol. 2021 Feb 25;9:642946. doi: 10.3389/fcell.2021.642946. eCollection 2021.
Noise-induced hearing loss (NIHL) is characterized by cellular damage to the inner ear, which is exacerbated by inflammation. High-mobility group box 1 (HMGB1), a representative damage-associated molecular pattern (DAMP), acts as a mediator of inflammation or an intercellular messenger according to its cellular localization. Blocking or regulating HMGB1 offers an attractive approach in ameliorating NIHL. However, the precise therapeutic intervention must be based on a deeper understanding of its dynamic molecular distribution and function in cochlear pathogenesis after acoustic trauma. Here, we have presented the spatiotemporal dynamics of the expression of HMGB1, exhibiting distribution variability in specific cochlear regions and cells following noise exposure. After gene manipulation, we further investigated the characteristics of cellular HMGB1 in HEI-OC1 cells. The higher cell viability observed in the HMGB1 knocked-down group after stimulation with HO indicated the possible negative effect of HMGB1 on cellular lifespan. In conclusion, this study demonstrated that HMGB1 is involved in NIHL pathogenesis and its molecular biology has essential and subtle influences, preserving a translational potential for pharmacological intervention.
噪声性听力损失（NIHL）的特征是内耳细胞受损，炎症会加剧这种损伤。高迁移率族蛋白B1（HMGB1）是一种典型的损伤相关分子模式（DAMP），根据其细胞定位，可作为炎症介质或细胞间信使。阻断或调节HMGB1为改善NIHL提供了一种有吸引力的方法。然而，精确的治疗干预必须基于对其在声创伤后耳蜗发病机制中的动态分子分布和功能的更深入理解。在这里，我们展示了HMGB1表达的时空动态，显示出噪声暴露后在特定耳蜗区域和细胞中的分布变异性。基因操作后，我们进一步研究了HEI-OC1细胞中细胞HMGB1的特征。HO刺激后，HMGB1敲低组观察到较高的细胞活力，这表明HMGB1对细胞寿命可能有负面影响。总之，本研究表明HMGB1参与NIHL发病机制，其分子生物学具有重要而微妙的影响，为药物干预保留了转化潜力。
