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Espin 在 Atoh1 过表达耳蜗上皮细胞中的静纤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.

机构信息

School of Medicine, South China University of Technology, Guangzhou, China.

Department of Otolaryngology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.

出版信息

Cell Prolif. 2023 Nov;56(11):e13483. doi: 10.1111/cpr.13483. Epub 2023 Apr 21.

DOI:10.1111/cpr.13483
PMID:37084708
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10623949/
Abstract

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.

摘要

哺乳动物的毛细胞（HCs）在受损后不能自发再生。Atoh1 的过表达可以促进出生后耳蜗内的 HC 再生，但再生的 HCs 不具有原位 HCs 的结构和功能特征。HCs 顶表面的静纤毛是声音传导的一级结构，功能性静纤毛的再生是功能性 HCs 再生的关键基础。Espin 作为一种肌动蛋白束蛋白，在静纤毛的发育和结构维持中发挥重要作用。在这里，我们发现，AAV-ie 上调 Espin 能够诱导 Atoh1 诱导的 HC 中肌动蛋白纤维的聚集，无论是在耳蜗类器官还是外植体中都是如此。此外，我们发现持续的 Atoh1 过表达会导致内源性和新形成的 HCs 中的静纤毛受损。相比之下，在内源性和再生的 HCs 中强制表达 Espin 能够消除持续 Atoh1 过表达引起的静纤毛损伤。我们的研究表明，Espin 的增强表达可以优化 Atoh1 诱导的 HCs 中静纤毛的发育过程，并减轻 Atoh1 过表达对内源性 HCs 造成的损伤。这些结果表明了一种有效的方法，可以诱导再生的 HCs 中静纤毛的成熟，并为通过支持细胞转分化实现功能性 HC 再生铺平道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ceb/10623949/22f2cde86c0c/CPR-56-e13483-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ceb/10623949/74ca37af37f2/CPR-56-e13483-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ceb/10623949/72b5e80152b7/CPR-56-e13483-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ceb/10623949/448f7b1799d4/CPR-56-e13483-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ceb/10623949/6d2bd7e59913/CPR-56-e13483-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ceb/10623949/22f2cde86c0c/CPR-56-e13483-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ceb/10623949/74ca37af37f2/CPR-56-e13483-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ceb/10623949/72b5e80152b7/CPR-56-e13483-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ceb/10623949/448f7b1799d4/CPR-56-e13483-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ceb/10623949/6d2bd7e59913/CPR-56-e13483-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ceb/10623949/22f2cde86c0c/CPR-56-e13483-g001.jpg

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