MECOM promotes supporting cell proliferation and differentiation in cochlea

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.