Deletion of Kcnj16 in Mice Does Not Alter Auditory Function

Lv, Jun; Fu, Xiaolong; Li, Yige; Hong, Guodong; Li, Peipei; Lin, Jing; Xun, Youfang; Fang, Lucheng; Weng, Weibin; Yue, Rongyu; Li, Geng-Lin; Guan, Bing; Li, He; Huang, Yideng; Chai, Renjie

doi:10.3389/fcell.2021.630361

Cited by 34 publications

(29 citation statements)

References 55 publications

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“…Sensorineural hearing loss is caused by many factors that impair hair cell and spiral ganglion neuron function [23][24][25][26][27][28], including ototoxic drugs, genetic factors, aging, noise exposure, and chronic cochlear infections [29][30][31][32][33]. A growing amount of evidence has demonstrated that PIN1 plays critical roles in aging-associated diseases [34][35][36][37][38][39].…”

Section: Discussionmentioning

confidence: 99%

PIN1 Protects Hair Cells and Auditory HEI‐OC1 Cells against Senescence by Inhibiting the PI3K/Akt/mTOR Pathway

Zhang

Liu

et al. 2021

Oxidative Medicine and Cellular Longevity

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A growing amount of evidence has confirmed the crucial role of the prolyl isomerase PIN1 in aging and age-related diseases. However, the mechanism of PIN1 in age-related hearing loss (ARHL) remains unclear. Pathologically, ARHL is primarily due to the loss and dysfunction of hair cells (HCs) and spiral ganglion cells (SGCs) in the cochlea. Therefore, in this study, we aimed to investigate the role of PIN1 in protecting hair cells and auditory HEI-OC1 cells from senescence. Enzyme-linked immunosorbent assays, immunohistochemistry, and immunofluorescence were used to detect the PIN1 protein level in the serum of ARHL patients and C57BL/6 mice in different groups, and in the SGCs and HCs of young and aged C57BL/6 mice. In addition, a model of HEI-OC1 cell senescence induced by H2O2 was used. Adult C57BL/6 mice were treated with juglone, or juglone and NAC, for 4 weeks. Interestingly, we found that the PIN1 protein expression decreased in the serum of patients with ARHL, in senescent HEI-OC1 cells, and in the cochlea of aged mice. Moreover, under H2O2 and juglone treatment, a large amount of ROS was produced, and phosphorylation of p53 was induced. Importantly, PIN1 expression was significantly increased by treatment with the p53 inhibitor pifithrin-α. Overexpression of PIN1 reversed the increased level of p-p53 and rescued HEI-OC1 cells from senescence. Furthermore, PIN1 mediated cellular senescence by the PI3K/Akt/mTOR signaling pathway. In vivo data from C57BL/6 mice showed that treatment with juglone led to hearing loss. Taken together, these findings demonstrated that PIN1 may act as a vital modulator in hair cell and HEI-OC1 cell senescence.

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Section: Discussionmentioning

confidence: 99%

PIN1 Protects Hair Cells and Auditory HEI‐OC1 Cells against Senescence by Inhibiting the PI3K/Akt/mTOR Pathway

Zhang

Liu

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…HCs in the inner ear cochlea function in transducing sound waves into electric signals [17][18][19][20][21], while supporting cells function in supporting the HCs and providing the potential pool for HC regeneration [22][23][24][25][26]. Damages from a variety of sources can impair HC function, including genetic factors, aging, ototoxic drugs, chronic cochlear infections, and noise exposure [19,[27][28][29][30][31]. In this study, we reported the protective effect of Clusterin deficiency against age-related hearing loss and drug-induced ototoxicity, which are both due to irreversible loss of sensory HCs [32][33][34][35][36] and degeneration of the spiral ganglion neurons (SGNs) [37][38][39][40][41][42].…”

Section: Discussionmentioning

confidence: 99%

Deletion of Clusterin Protects Cochlear Hair Cells against Hair Cell Aging and Ototoxicity

et al. 2021

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Hearing loss is a debilitating disease that affects 10% of adults worldwide. Most sensorineural hearing loss is caused by the loss of mechanosensitive hair cells in the cochlea, often due to aging, noise, and ototoxic drugs. The identification of genes that can be targeted to slow aging and reduce the vulnerability of hair cells to insults is critical for the prevention of sensorineural hearing loss. Our previous cell-specific transcriptome analysis of adult cochlear hair cells and supporting cells showed that Clu, encoding a secreted chaperone that is involved in several basic biological events, such as cell death, tumor progression, and neurodegenerative disorders, is expressed in hair cells and supporting cells. We generated Clu-null mice (C57BL/6) to investigate its role in the organ of Corti, the sensory epithelium responsible for hearing in the mammalian cochlea. We showed that the deletion of Clu did not affect the development of hair cells and supporting cells; hair cells and supporting cells appeared normal at 1 month of age. Auditory function tests showed that Clu-null mice had hearing thresholds comparable to those of wild-type littermates before 3 months of age. Interestingly, Clu-null mice displayed less hair cell and hearing loss compared to their wildtype littermates after 3 months. Furthermore, the deletion of Clu is protected against aminoglycoside-induced hair cell loss in both in vivo and in vitro models. Our findings suggested that the inhibition of Clu expression could represent a potential therapeutic strategy for the alleviation of age-related and ototoxic drug-induced hearing loss.

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“…HC transduces the sound waves into electric signals (Qi et al, 2019), while SGNs transfer these signals into the auditory cortex to have the hearing ability (Guo et al, 2016, 2019, 2020). WHO reported that 466 million people are suffering with hearing loss worldwide, caused by genetic factors, infectious diseases, chronic cochlear infections, aging, exposure to noise, and ototoxic drugs (He et al, 2017(He et al, , 2020Tan et al, 2019;Zhang et al, 2020;Zhou et al, 2020;Lv et al, 2021); for children from 6 to 19 years old, the estimated CSSD incidence was 0.7-0.8%. In this study, we reported a Bama miniature pedigree with high and stable incidence of CSSD, which reached 46.67% under the mating mode of paternal CSSD with maternal CSSD pigs.…”

Section: Discussionmentioning

confidence: 99%

A Porcine Congenital Single-Sided Deafness Model, Its Population Statistics and Degenerative Changes

Ren

Zheng

et al. 2021

Front. Cell Dev. Biol.

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ObjectiveTo describe and study the population statistics, hearing phenotype, and pathological changes of a porcine congenital single-sided deafness (CSSD) pedigree.MethodsClick auditory brainstem response (ABR), full-frequency ABR, and distortion product otoacoustic emission (DPOAE) were used to assess the hearing phenotype of the strain. Tympanogram was used to assess the middle ear function since birth. Celloidin embedding–hematoxylin–eosin (CE-HE) stain and scanning electron microscopy (SEM) were used to study the pathological changes of cochlear microstructures. Chi-square analysis was used to analyze the relation between hearing loss and other phenotypes.ResultsThe mating mood of CSSD with CSSD was most efficient in breeding-targeted CSSD phenotype (47.62%), and the prevalence of CSSD reached 46.67% till the fifth generation, where 42.22% were bilateral hearing loss (BHL) and 9.00% were normal hearing (NH) individuals. Hearing loss was proved to have no relation with coat color (P = 0.0841 > 0.05) and gender (P = 0.4621 > 0.05) by chi-square analysis. The deaf side of CSSD offspring in the fifth generation had no relation with that of their maternal parent (P = 0.2387 > 0.05). All individuals in this strain exhibited congenital severe to profound sensorineural hearing loss with no malformation and dysfunction of the middle ear. The good hearing ear of CSSD stayed stable over age. The deaf side of CSSD and BHL presented cochlear and saccular degeneration, and the hair cell exhibited malformation since birth and degenerated from the apex to base turn through time. The pathology in BHL cochlea progressed more rapidly than CSSD and till P30, the hair cell had been totally gone. The stria vascularis (SV) was normal since birth and degenerated through time and finally exhibited disorganization of three layers of cells.ConclusionThis inbred porcine strain exhibited high and stable prevalence of CSSD, which highly resembled human non-syndromic CSSD disease. This porcine model could be used to further explore the etiology of CSSD and serve as an ideal tool for the studies of the effects of single-sided hearing deprivation on neural, cognitive, and behavioral developments and the benefits brought by CI in CSSD individuals.

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Deletion of Kcnj16 in Mice Does Not Alter Auditory Function

Cited by 34 publications

References 55 publications

PIN1 Protects Hair Cells and Auditory HEI‐OC1 Cells against Senescence by Inhibiting the PI3K/Akt/mTOR Pathway

PIN1 Protects Hair Cells and Auditory HEI‐OC1 Cells against Senescence by Inhibiting the PI3K/Akt/mTOR Pathway

Deletion of Clusterin Protects Cochlear Hair Cells against Hair Cell Aging and Ototoxicity

A Porcine Congenital Single-Sided Deafness Model, Its Population Statistics and Degenerative Changes

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