Peipei Chen , Na Zuo , Cheng Wu , Jun Ma , Yao Li , Junfei Gu , Wen Li , Shaofeng Liu
{"title":"MECOM promotes supporting cell proliferation and differentiation in cochlea","authors":"Peipei Chen , Na Zuo , Cheng Wu , Jun Ma , Yao Li , Junfei Gu , Wen Li , Shaofeng Liu","doi":"10.1016/j.joto.2021.11.002","DOIUrl":null,"url":null,"abstract":"<div><p>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 <strong>(</strong><em>MECOM)</em> 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, <em>MECOM</em> plays an essential role in neurogenesis and craniofacial development. However, the role of <em>MECOM</em> 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 <em>MECOM</em> 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 <em>MECOM</em> 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 <em>MECOM</em> in SC proliferation and trans-differentiation into HCs, as well as its regulation. The interaction between <em>MECOM</em>, Wnt, Notch and the TGF-β signaling may provide a feasible approach to induce the regeneration of HCs.</p></div>","PeriodicalId":37466,"journal":{"name":"Journal of Otology","volume":null,"pages":null},"PeriodicalIF":1.4000,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/64/82/main.PMC9349018.pdf","citationCount":"3","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Otology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1672293021000611","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"OTORHINOLARYNGOLOGY","Score":null,"Total":0}
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.
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.