Atoh1-overexpressed cochlear epithelium中Espina在立毛再生和保护中的作用。
The role of Espin in the stereocilia regeneration and protection in Atoh1-overexpressed cochlear epithelium.
发表日期：2023 Apr 21
作者：
Xuechun Yang, Jieyu Qi, Liyan Zhang, Fangzhi Tan, Hongming Huang, Chunlai Xu, Yong Cui, Renjie Chai, Peina Wu
来源：
CELL PROLIFERATION
摘要：
哺乳动物的毛细胞（HCs）在遭受损伤后无法自行再生。Atoh1过度表达可以促进后生的耳蜗中HC的再生，但是再生的HC并不具备固有HC的结构和功能特性。HC顶端表面的毛细胞丝是声音传导的第一层结构，恢复功能性的毛细胞丝是再现功能性HC的关键基础。作为一个肌动蛋白束缚蛋白，Espin在毛细胞丝的发育和结构维护中起着重要作用。本研究发现，AAV-ie诱导下的Espin上调能够在cochlear organoids和外植体中诱导Atoh1诱导的HC中的肌动蛋白纤维聚集。此外，本研究发现，持续的Atoh1过度表达会导致内源性和新形成的HC的毛细胞丝受损。相反，内源性和再生性HC中强制表达的Espin能够消除持续的Atoh1过度表达引起的毛细胞丝损伤。我们的研究表明，Espin的增强表达可优化Atoh1诱导的HC毛细胞丝的发育过程，并减轻Atoh1过度表达引起的本地HC损伤。这些结果提供了一种有效的方法来诱导再生HC毛细胞丝的成熟，为支持细胞转分化引导功能性HC再生铺平道路。© 2023 The Authors.由北京干细胞和再生医学研究所和约翰·威立出版社发表的细胞增殖。
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.© 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.