The role of Espin in the stereocilia regeneration and protection in Atoh1-overexpressed cochlear epithelium.
The role of Espin in the stereocilia regeneration and protection in Atoh1-overexpressed cochlear epithelium.
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DOI：
10.1111/cpr.13483
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发表时间：
2023-11
影响因子：
8.5
通讯作者：
中科院分区：
文献类型：
--
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哺乳动物的毛细胞（HC）在受损后不能自发再生。Atoh 1过表达可促进生后耳蜗毛细胞再生，但再生毛细胞不具备原位毛细胞的结构和功能特征。毛细胞顶面的静纤毛是声传导的第一级结构，功能性静纤毛的再生是毛细胞再生的重要基础。Espin作为一种肌动蛋白捆绑蛋白，在静纤毛的发育和结构维持中起着重要作用。在这里，我们发现AAV-ie上调Espin能够诱导耳蜗类器官和外植体中Atoh 1诱导的HC中肌动蛋白纤维的聚集。此外，我们发现持续Atoh 1过度表达导致内源性和新形成的毛细胞的静纤毛受损。相比之下，内源性和再生性毛细胞中Espin的强制表达能够消除持续Atoh 1过表达引起的静纤毛损伤。我们的研究表明，Espin的表达增强可以优化Atoh 1诱导的毛细胞中静纤毛的发育过程，并可以减轻Atoh 1过表达诱导的天然毛细胞损伤。这些结果表明，一种有效的方法来诱导静纤毛在再生HC的成熟，并通过支持细胞转分化为功能性HC再生铺平道路。持续Atoh 1过表达导致内源性和再生毛细胞（HC）中的静纤毛受损。Espin的表达增强优化了Atoh 1诱导的HC中静纤毛的发育过程。Espin的上调减弱Atoh 1过表达引起的静纤毛损伤。
Hair cells (HCs) in mammals cannot spontaneously regenerate after damage. Atoh1 overexpression can promote HC regeneration in the postnatal cochlea, but the regenerated HCs do not possess the structural and functional characteristics of HCs in situ. The stereocilia on the apical surface of HCs are the first‐level structure for sound conduction, and regeneration of functional stereocilia is the key basis for the reproduction of functional HCs. Espin, as an actin bundling protein, plays an important role in the development and structural maintenance of the stereocilia. Here, we found that the upregulation of Espin by AAV‐ie was able to induced the aggregation of actin fibres in Atoh1‐induced HCs in both cochlear organoids and explants. In addition, we found that persistent Atoh1 overexpression resulted in impaired stereocilia in both endogenous and newly formed HCs. In contrast, the forced expression of Espin in endogenous and regenerative HCs was able to eliminate the stereocilia damage caused by persistent Atoh1 overexpression. Our study shows that the enhanced expression of Espin can optimize the developmental process of stereocilia in Atoh1‐induced HCs and can attenuate the damage to native HCs induced by Atoh1 overexpression. These results suggest an effective method to induce the maturation of stereocilia in regenerative HCs and pave the way for functional HC regeneration via supporting cell transdifferentiation. Persistent Atoh1 overexpression results in impaired stereocilia in both endogenous and regenerative hair cells (HCs). The enhanced expression of Espin optimizes the developmental process of stereocilia in Atoh1‐induced HCs. The upregulation of Espin attenuates the damage to stereocilia caused by Atoh1 overexpression.
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影响因子：
64.5
作者：
Oshima K;Shin K;Diensthuber M;Peng AW;Ricci AJ;Heller S
通讯作者：
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12.4
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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.