Regeneration of stereocilia of hair cells by forced Atoh1 expression in the adult mammalian cochlea.
Regeneration of stereocilia of hair cells by forced Atoh1 expression in the adult mammalian cochlea.
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DOI：
10.1371/journal.pone.0046355
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
He DZ
中科院分区：
文献类型：
--
作者：
Yang SM;Chen W;Guo WW;Jia S;Sun JH;Liu HZ;Young WY;He DZ
机械感觉毛细胞的标志是立体纤毛，在那里机械刺激被转换成电信号。这些脆弱的纤毛容易受到声损伤和耳毒性药物的影响。虽然低等脊椎动物和哺乳动物前庭系统的毛细胞可以自发地再生失去的立体纤毛，但哺乳动物耳蜗的毛细胞不再保留这种能力。我们探索了通过耳蜗接种携带Atoh1（毛细胞分化的关键基因）的病毒载体，在噪声耳聋的豚鼠耳蜗中再生立体纤毛的可能性。暴露于模拟枪声中导致60-70分贝的听力损失，以及沿整个耳蜗长度的内外部毛细胞的立体纤毛束的广泛损伤和损失。然而，大多数受伤的毛细胞在创伤后的10天内仍留在Corti的器官中。在噪声暴露后第7天，将携带egfp标记的Atoh1基因的病毒载体通过圆窗接种于耳蜗。接种后一个月测量的听性脑干反应显示，听力阈值有了显著提高。扫描电镜显示，经Atoh1处理后，受损/丢失的立体纤毛束得到修复或再生，提示Atoh1能够诱导受损或丢失的立体纤毛的修复/再生。因此，我们的研究揭示了Atoh1作为促进成年哺乳动物耳蜗立体纤毛修复/再生和维持受损毛细胞的关键基因的新作用。因此，如果在毛细胞死亡之前进行以atoh1为基础的基因治疗，就有可能治疗噪声性听力损失。
The hallmark of mechanosensory hair cells is the stereocilia, where mechanical stimuli are converted into electrical signals. These delicate stereocilia are susceptible to acoustic trauma and ototoxic drugs. While hair cells in lower vertebrates and the mammalian vestibular system can spontaneously regenerate lost stereocilia, mammalian cochlear hair cells no longer retain this capability. We explored the possibility of regenerating stereocilia in the noise-deafened guinea pig cochlea by cochlear inoculation of a viral vector carrying Atoh1, a gene critical for hair cell differentiation. Exposure to simulated gunfire resulted in a 60–70 dB hearing loss and extensive damage and loss of stereocilia bundles of both inner and outer hair cells along the entire cochlear length. However, most injured hair cells remained in the organ of Corti for up to 10 days after the trauma. A viral vector carrying an EGFP-labeled Atoh1 gene was inoculated into the cochlea through the round window on the seventh day after noise exposure. Auditory brainstem response measured one month after inoculation showed that hearing thresholds were substantially improved. Scanning electron microscopy revealed that the damaged/lost stereocilia bundles were repaired or regenerated after Atoh1 treatment, suggesting that Atoh1 was able to induce repair/regeneration of the damaged or lost stereocilia. Therefore, our studies revealed a new role of Atoh1 as a gene critical for promoting repair/regeneration of stereocilia and maintaining injured hair cells in the adult mammal cochlea. Atoh1-based gene therapy, therefore, has the potential to treat noise-induced hearing loss if the treatment is carried out before hair cells die.
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DOI：
10.1002/neu.10002
发表时间：
2002-02-05
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
Gale, JE;Meyers, JR;Corwin, JT
通讯作者：
Corwin, JT
DOI：
10.1073/pnas.97.22.11722
发表时间：
2000-10-24
影响因子：
11.1
作者：
Baird, RA;Burton, MD;Naeger, RA
通讯作者：
Naeger, RA
影响因子：
64.8
作者：
BenArie, N;Bellen, HJ;Zoghbi, HY
通讯作者：
Zoghbi, HY
影响因子：
2.4
作者：
HAMERNIK, RP;PATTERSON, JH;SALVI, RJ
通讯作者：
SALVI, RJ
影响因子：
64.8
作者：
Gubbels, Samuel P.;Woessner, David W.;Mitchell, John C.;Ricci, Anthony J.;Brigande, John V.
通讯作者：
Brigande, John V.