The purpose of this study was to clarify the relationship among X-box-binding protein 1 unspliced, spliced (XBP1u, s), Forkhead box O1 (FoxO1) and autophagy in the auditory cells under endoplasmic reticulum (ER) stress. In addition, the relationship between ER stress that causes unfolded protein response (UPR) and autophagy was also investigated. The present study reported ER stress induction by tunicamycin treatment that resulted in IRE1α-mediated XBP1 mRNA splicing and autophagy. XBP1 mRNA splicing and FoxO1 were found to be involved in ER stress-induced autophagy. This inference was based on the observation that the expression of LC3-II was suppressed by knockdown of IRE1α, XBP1 or FoxO1. In addition, XBP1u was found to interact with XBP1s in auditory cells under ER stress, functioning as a negative feedback regulator that was based on two important findings. Firstly, there was a significant inverse correlation between XBP1u and XBP1s expressions, and secondly, the expression of XBP1 protein showed different dynamics compared to the XBP1 mRNA level. Furthermore, our results regarding the relationship between XBP1 and FoxO1 by small interfering RNA (siRNA) paradoxically showed negative regulation of FoxO1 expression by XBP1. Our findings revealed that the XBP1-FoxO1 interaction regulated the ER stress-induced autophagy in auditory cells.

中文翻译：

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XBP1-FoxO1相互作用调节听觉细胞中内质网应激诱导的自噬。

本研究的目的是阐明内质网（ER）胁迫下听觉细胞中未剪接，剪接的X-box结合蛋白1（XBP1u，s），叉头盒O1（FoxO1）与自噬之间的关系。此外，还研究了导致未反应蛋白反应（UPR）的内质网应激与自噬之间的关系。本研究报道了衣霉素处理引起的ER应激诱导，导致IRE1α介导的XBP1 mRNA剪接和自噬。发现XBP1 mRNA剪接和FoxO1参与内质网应激诱导的自噬。该推论基于以下观察：通过敲低IRE1α，XBP1或FoxO1抑​​制LC3-II的表达。此外，还发现XBP1u与内质网应激的听觉细胞中的XBP1s相互作用，基于两个重要发现，作为负反馈调节器。首先，XBP1u和XBP1s的表达之间存在显着的负相关，其次，与XBP1 mRNA的水平相比，XBP1蛋白的表达表现出不同的动力学特性。此外，我们关于小干扰RNA（siRNA）对XBP1和FoxO1之间关系的研究结果矛盾地显示，XBP1对FoxO1表达的负调控。我们的发现表明，XBP1-FoxO1相互作用调节了听觉细胞中ER应激诱导的自噬。我们关于小干扰RNA（siRNA）与XBP1和FoxO1之间关系的研究结果矛盾地显示XBP1对FoxO1表达的负调控。我们的发现表明，XBP1-FoxO1相互作用调节了听觉细胞中ER应激诱导的自噬。我们关于小干扰RNA（siRNA）与XBP1和FoxO1之间关系的研究结果矛盾地显示XBP1对FoxO1表达的负调控。我们的发现表明，XBP1-FoxO1相互作用调节了听觉细胞中ER应激诱导的自噬。