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  • Title: Ectopic expression of ROR1 prevents cochlear hair cell loss in guinea pigs with noise-induced hearing loss.
    Author: Zhang J, Zhang W, Zhang Q.
    Journal: J Cell Mol Med; 2020 Aug; 24(16):9101-9113. PubMed ID: 34008309.
    Abstract:
    Noise-induced hearing loss (NIHL) is one of the most frequent disabilities in industrialized countries. Evidence shows that hair cell loss in the auditory end organ is responsible for the majority of various ear pathological conditions. The functional roles of the receptor tyrosine kinase ROR1 have been underscored in various tumours. In this study, we evaluated the ability of ROR1 to influence cochlear hair cell loss of guinea pigs with NIHL. The NIHL model was developed in guinea pigs, with subsequent measurement of the auditory brainstem response (ABR). Gain-of-function experiments were employed to explore the role of ROR1 in NIHL. The interaction between ROR1 and Wnt5a and their functions in the cochlear hair cell loss were further analysed in response to alteration of ROR1 and Wnt5a. Guinea pigs with NIHL demonstrated elevated ABR threshold and down-regulated ROR1, Wnt5a and NF-κB p65. The up-regulation of ROR1 was shown to decrease the cochlear hair cell loss and the expression of pro-apoptotic gene (Bax, p53) in guinea pig cochlea, but promoted the expression of anti-apoptotic gene (Bcl-2) and the fluorescence intensity of cleaved-caspase-3. ROR1 interacted with Wnt5a to activate the NF-κB signalling pathway through inducing phosphorylation and translocation of p65. Furthermore, Wnt5a overexpression decreased the cochlear hair cell loss. Collectively, this study suggested the protection of overexpression of ROR1 against cochlear hair cell loss in guinea pigs with NIHL via the Wnt5a-dependent NF-κB signalling pathway.
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