Molecular Behavior of HMGB1 in the Cochlea Following Noise Exposure and in vitro.

Lili Xiao,Chengqi Liu,Zhong Zheng,Yanmei Feng,Ying Shen,Guang Yang,Liang Xia,Yan Sun

doi:10.3389/fcell.2021.642946

Abstract

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 H2O2 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.

Highlights

Hearing loss is often induced by loss of sensory hair cells (HCs) in the inner ear cochlea, which functions in the transduction of sound waves into electric signals (Zhu et al, 2018; Liu et al, 2019; Qi et al, 2020)
Post hoc pairwise tests showed a significant elevation of the auditory brainstem response (ABR) threshold shift at 4 kHz in the 1day post-noise exposure (1dPNE) group as compared with those in the 3dPNE, 7dPNE, and 14dPNE groups (t = 4.286, 6.231, 9.710, respectively, p < 0.001), as well as at 8 kHz with only the 14dPNE group (t = 3.109, p = 0.017)
We found that the level of High-mobility group box 1 (HMGB1) increased significantly in the 3dPNE group (t = 3.706, p = 0.028) but not in the 1dPNE group (t = 1.874, p = 0.315) compared with the control group

Summary

Introduction

Hearing loss is often induced by loss of sensory hair cells (HCs) in the inner ear cochlea, which functions in the transduction of sound waves into electric signals (Zhu et al, 2018; Liu et al, 2019; Qi et al, 2020). Noise-induced hearing loss (NIHL) is the most common type of sensorineural hearing loss, ranking first among occupational diseases, seriously affecting the lives of patients, and greatly increasing the social burden (Carroll et al, 2017; Murphy et al, 2018). Damage-associated molecular patterns (DAMPs), the cellular byproducts of damage, are known to play an essential role in this inflammation. They could stimulate pattern recognition receptors, leading to the rapid release of proinflammatory cytokines and production of ROS, insulting sensorineural cells (Tang et al, 2012; He et al, 2017; Wood and Zuo, 2017). The type and function of DAMPs in the cochlea following acoustic trauma is rarely clear

Methods

Results

Conclusion