Cochlin Deficiency Protects Against Noise-Induced Hearing Loss.
Cochlin Deficiency Protects Against Noise-Induced Hearing Loss.
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Cochlin缺乏可防止噪声引起的听力损失。
DOI：
10.3389/fnmol.2021.670013
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发表时间：
2021
影响因子：
4.8
通讯作者：
Stankovic KM
中科院分区：
文献类型：
--
作者：
Seist R;Landegger LD;Robertson NG;Vasilijic S;Morton CC;Stankovic KM
Cochlin是内耳中含量最丰富的蛋白质。为了研究其在噪声创伤反应中的作用，我们将青春期野生型(COCH+/+)和cochlin基因敲除(COCH-/-)小鼠暴露在噪声(8-16 kHz，103dBSPL，2 h)中，这些噪声会导致永久性的阈值漂移和毛细胞丢失。噪声暴露两周后，与Coch+/+小鼠相比，Coch-/-小鼠在噪声诱导的听觉阈值和毛细胞丢失方面的升高要小得多，这与Cochlin缺乏提供保护以免受噪声创伤的情况一致。对Coch-/-小鼠和Coch+/+仔鼠的听性脑干反应(ABR)和失真产物耳声发射(DPOAEs)的噪声前暴露阈值进行了比较，发现Coch-/-小鼠的听性脑干反应(ABR)和失真产物耳声发射(DPOAE)的阈值有轻微而显著的升高，总体上与Coch-/-小鼠的小幅传导性听力损失一致。我们定量地表明，与未暴露的小鼠相比，噪声暴露后野生型小鼠外淋巴液中Cochlin的促炎成分LCCL上调，Adamts4编码的催化LCCL释放的酶aggrecanase1也是如此。我们进一步表明，噪声暴露后，耳蜗癌基因敲除小鼠外淋巴液和耳蜗软组织中促炎症细胞因子的上调低于野生型小鼠。综上所述，我们的数据首次表明，Cochlin缺乏会导致传导性听力损失，从而保护人们免受噪声创伤的生理和分子影响。
Cochlin is the most abundant protein in the inner ear. To study its function in response to noise trauma, we exposed adolescent wild-type (Coch+/+) and cochlin knock-out (Coch–/–) mice to noise (8–16 kHz, 103 dB SPL, 2 h) that causes a permanent threshold shift and hair cell loss. Two weeks after noise exposure, Coch–/– mice had substantially less elevation in noise-induced auditory thresholds and hair cell loss than Coch+/+ mice, consistent with cochlin deficiency providing protection from noise trauma. Comparison of pre-noise exposure thresholds of auditory brain stem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs) in Coch–/– mice and Coch+/+ littermates revealed a small and significant elevation in thresholds of Coch–/– mice, overall consistent with a small conductive hearing loss in Coch–/– mice. We show quantitatively that the pro-inflammatory component of cochlin, LCCL, is upregulated after noise exposure in perilymph of wild-type mice compared to unexposed mice, as is the enzyme catalyzing LCCL release, aggrecanase1, encoded by Adamts4. We further show that upregulation of pro-inflammatory cytokines in perilymph and cochlear soft-tissue after noise exposure is lower in cochlin knock-out than wild-type mice. Taken together, our data demonstrate for the first time that cochlin deficiency results in conductive hearing loss that protects against physiologic and molecular effects of noise trauma.
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影响因子：
3.8
作者：
Rhyu HJ;Bae SH;Jung J;Hyun YM
通讯作者：
Hyun YM
影响因子：
5.3
作者：
Kujawa, SG;Liberman, MC
通讯作者：
Liberman, MC
影响因子：
3.7
作者：
Jensen JB;Lysaght AC;Liberman MC;Qvortrup K;Stankovic KM
通讯作者：
Stankovic KM
DOI：
10.1523/jneurosci.2845-09.2009
发表时间：
2009-11-11
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kujawa SG;Liberman MC
通讯作者：
Liberman MC
影响因子：
2.4
作者：
CODY, AR;JOHNSTONE, BM
通讯作者：
JOHNSTONE, BM