Preliminary Study Of The Role Of XBP1 And ATF4-mediated Endoplasmic Reticulum Stress In Noise-induced Hearing Loss

Deafness is the most common sensory defect,which seriously affects learning,communication and quality of life.With the advent of the industrial era,noise has increasingly become an important factor affecting people’s normal life and work and rest.Long-term exposure to noise environment will cause serious damage to people’s hearing,resulting in noise-induced hearing loss.At present,the mechanism of noise-induced hearing loss is not very clear,which hinders the clinical help for related patients.Endoplasmic reticulum(ER),as an important organelle,plays an important role in protein and other macromolecules synthesis,processing and calcium homeostasis.Endoplasmic reticulum dysfunction,unfolded or misfolded protein accumulation can be caused by specific physiological or pathological conditions,which will induce ER stress.ER stress activates three major signaling pathways:IRE1α-XBP1,PERK-ATF4 and ATF6α,blocking protein synthesis and activating chaperone protein expression to alleviate ER dysfunction.Excessive and uncontrolled ER stress can cause apoptosis.Studies have shown that endoplasmic reticulum stress related markers in the cochlea of guinea pigs and mice were significantly changed after noise exposure,suggesting that ER stress may be associated with noise-induced hearing loss.In this study,Xbp1 knockout mice and Atf4 knockout mice were used to investigate the role of Xbp1 and Atf4 mediated endoplasmic reticulum stress in noise-induced hearing loss.Our results showed that Xbp1 knockout mice and Atf4 knockout mice had normal hearing under quiet environment,indicating that these two gene knockout mice did not affect hearing by themselves.Endoplasmic reticulum stress levels in the inner ear of Xbp1 knockout mice and Atf4 knockout mice were significantly reduced under noise exposure compared with control mice,which is consistent with the fact that Xbpl and Atf4 are important regulatory proteins of endoplasmic reticulum stress.Surprisingly,there was no significant difference in the changes of hearing threshold in Xbp1 knockout mice and Atf4 knockout mice under noise exposure compared with control mice,suggesting that ER stress mediated by XBP1 and ATF4 may not play an important role in the development of noise-induced hearing loss.In conclusion,our preliminary results suggest that ER stress mediated by XBP1 and ATF4 may not play an important role in the development of noise-induced hearing loss.Endoplasmic reticulum stress is a complex process,which may be affected by a variety of conditions,such as mouse strains,noise conditions,etc.,and its specific function in noise-induced hearing loss needs further study.