骨形态发生蛋白4在内耳发育及在毛细胞与螺旋神经节细胞再生中的研究进展

Advances in the role of bone morphogenetic protein⁃4 in inner ear development and regeneration of hair and spiral ganglion cells

听力损失是人类最常见的感觉缺陷,主要涉及到毛细胞(HCs)和螺旋神经节细胞(SGCs)的损失等。在内耳发育过程中,骨形态发生蛋白4(BMP4)的表达具有时序性和特异性,并且通过调控分泌蛋白Tsukushin(TSK)、性别决定相关基因簇2蛋白(SOX2)等细胞因子,与WNT和SHH等信号通路之间相互作用,参与耳泡的诱导、前庭和耳蜗等器官的形成、HCs和SGCs等细胞的分化过程。此外,近些年在哺乳动物与非哺乳动物的耳蜗外植体中,发现BMP4在HCs和SGCs的再生中起重要作用。综述BMP4调控内耳发育、诱导HCs和SGCs再生的作用,以及相关的研究进展,以期为HCs和SGCs再生相关机制的阐明奠定基础,为听力损失的治疗带来新的思路与策略。

Hearing loss,the most common sensory defect in humans,involves the loss of hair cells(HCs)and spiral ganglion cells(SGCs).During the development of the inner ear,the specific and temporal expression of(bone morphogenetic protein-4,BMP4)regulates the expression of the Tsukushin and gender determination⁃related gene cluster 2 proteins and other cytokines.BMP4 inter⁃acts with the Wnt and Shh signaling pathways and is involved in the induction of ear vesicles,formation of vestibular and cochlear organs,and differentiation of HCs and SGCs.Furthermore,in recent years BMP4 has been found to play an important role in the regeneration of HCs and SGCs in both mammalian and non⁃mammalian cochlear explants.This study reviews the role of BMP4 in regulating inner ear development and inducing the regeneration of HCs and SGCs,as well as progress in related research,to lay a foundation for elucidating mechanisms related to regeneration and bring developing new strategies to treat hearing loss.