MECOM promotes supporting cell proliferation and differentiation in cochlea

IF 1.4 Q2 OTORHINOLARYNGOLOGY
Peipei Chen , Na Zuo , Cheng Wu , Jun Ma , Yao Li , Junfei Gu , Wen Li , Shaofeng Liu
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引用次数: 3

Abstract

Permanent damage to hair cells (HCs) is the leading cause of sensory deafness. Supporting cells (SCs) are essential in the restoration of hearing in mammals because they can proliferate and differentiate to HCs. MDS1 and EVI1 complex locus (MECOM) is vital in early development and cell differentiation and regulates the TGF-β signaling pathway to adapt to pathophysiological events, such as hematopoietic proliferation, differentiation and cells death. In addition, MECOM plays an essential role in neurogenesis and craniofacial development. However, the role of MECOM in the development of cochlea and its way to regulate related signaling are not fully understood. To address this problem, this study examined the expression of MECOM during the development of cochlea and observed a significant increase of MECOM at the key point of auditory epithelial morphogenesis, indicating that MECOM may have a vital function in the formation of cochlea and regeneration of HCs. Meanwhile, we tried to explore the possible effect and potential mechanism of MECOM in SC proliferation and HC regeneration. Findings from this study indicate that overexpression of MECOM markedly increases the proliferation of SCs in the inner ear, and the expression of Smad3 and Cdkn2b related to TGF signaling is significantly down-regulated, corresponding to the overexpression of MECOM. Collectively, these data may provide an explanation of the vital function of MECOM in SC proliferation and trans-differentiation into HCs, as well as its regulation. The interaction between MECOM, Wnt, Notch and the TGF-β signaling may provide a feasible approach to induce the regeneration of HCs.

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MECOM促进耳蜗支持细胞增殖和分化
毛细胞永久性损伤(HCs)是感觉耳聋的主要原因。支持细胞(SCs)在哺乳动物听力恢复中是必不可少的,因为它们可以增殖并分化为肝细胞。MDS1和EVI1复合体位点(MECOM)在早期发育和细胞分化中起着至关重要的作用,并调节TGF-β信号通路以适应造血增殖、分化和细胞死亡等病理生理事件。此外,MECOM在神经发生和颅面发育中起着重要作用。然而,MECOM在耳蜗发育中的作用及其调控相关信号的方式尚不完全清楚。为了解决这一问题,本研究检测了耳蜗发育过程中MECOM的表达,发现在听觉上皮形态发生的关键时刻,MECOM的表达显著增加,提示MECOM可能在耳蜗的形成和hc的再生中具有重要的功能。同时,我们试图探讨MECOM在SC增殖和HC再生中的可能作用和潜在机制。本研究结果表明,MECOM过表达可显著增加内耳SCs的增殖,与TGF信号相关的Smad3和Cdkn2b表达显著下调,与MECOM过表达相对应。总的来说,这些数据可以解释MECOM在SC增殖和向hc的反分化中的重要功能及其调控。MECOM、Wnt、Notch与TGF-β信号的相互作用可能为诱导hc再生提供了一种可行的途径。
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来源期刊
Journal of Otology
Journal of Otology Medicine-Otorhinolaryngology
CiteScore
2.70
自引率
0.00%
发文量
461
审稿时长
18 days
期刊介绍: Journal of Otology is an open access, peer-reviewed journal that publishes research findings from disciplines related to both clinical and basic science aspects of auditory and vestibular system and diseases of the ear. This journal welcomes submissions describing original experimental research that may improve our understanding of the mechanisms underlying problems of basic or clinical significance and treatment of patients with disorders of the auditory and vestibular systems. In addition to original papers the journal also offers invited review articles on current topics written by leading experts in the field. The journal is of primary importance for all scientists and practitioners interested in audiology, otology and neurotology, auditory neurosciences and related disciplines. Journal of Otology welcomes contributions from scholars in all countries and regions across the world.
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