Noise Induced Matrix Metalloproteinases Changes And Its Effect On Blood-labyrinth Barrier

Noise causes permanent damage to the auditory system, and is an importantoccupational hazard in modern industrial societies. Studies on themolecular mechanisms of noise-induced hearing loss can help us betterunderstand the pathophysiology of noise induced auditory system injury,and take more effective actions for hearing conservation and noise-inducedhearing loss (NIHL) treatment.The blood-labyrinth barrier (BLB) in the stria vascular of cochlea isessential for maintaining the fluid balance, ion transportation andendocochlear potential (EP) in the inner ear. The injury of the BLB is oneof the early characteristics of noise induced damage to cochlea. Previousstudies had found that matrix metalloproteinases (MMPs) were widelydistributed in the cochlea. MMPs are capable of degrading the extracellularmatrix (ECM), and may play an important role in preserving the normalfunction of the inner ear.On the basis of successfully construction of an noise-induced hearing lossanimal model, we investigated the distribution of MMP-2and MMP-9in thestria vascular of cochlea in control and noise exposure guinea pigs, andobserved the consequent changes of tight junction protein zona occluden-1(ZO-1) and capillary permeability by the use of immunohischamistry,immunofluorescence, cochlear surface preparation, temporal bone frozensections and confocal laser scanning microscopy. We found that MMP-2, MMP-9in the control guinea pigs mainly distributed in the marginal cell and basal cell of stria vascular, and their expressions significantly increased inthe three layers of stria vascular (marginal cell, intermediate cell, basalcell) after noise exposure. And the structure of ZO-1in the marginal cellwas found to become loose, with some breaks appeared. Meanwhile asignificantly increase serum protein leakage out of capillaries in striavascular occurred,.We then mapped and quantified the transcripts of MMPs and tight junctionproteins in the stria vascular of cochlea in control and noise exposureguinea pigs by RNA-seq, and found that the gene expression pattern of thecontrol group was notably different from that of the noise exposure group.There were15MMPs related gene expressed in the control group, and afternoise exposure,10of15MMPs gene were up-regulated, with5down-regulated.In the control group there were3TIMPs gene(TIMP1-3), which up-regulatedafter noise exposure. While a little expression of TIMP-4gene was alsofound after noise exposure. The tight junction (TJ) proteins(ZO-1,ZO-2,Occludin,Claudin-5and VE-Cadherin) were found in the controlgroup, which was in consistent of the function of the BLB. The expressionlevel of these TJs proteins appeared up-regulating after acousticoverstimulation.We speculate that MMPs/TIMPs balance play an indispensable role inmaintaining the normal function of the BLB. The increase expression of MMPsafter noise exposure could possibly be the reason of the tight junctionproteins destruction and the increase permeability of capillaries in thestria vascular. Yet the process of noise induced damage to the BLB is verycomplicated, with a number of regulatory mechanisms involed and needfurther exploration.