XBP1-FoxO1 interaction regulates ER stress-induced autophagy in auditory cells

Abstract 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 pr...

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Autores principales:	Akihiro Kishino, Ken Hayashi, Chiaki Hidai, Takeshi Masuda, Yasuyuki Nomura, Takeshi Oshima
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ce771875e796400bbd76d30f7052ea99
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spelling	oai:doaj.org-article:ce771875e796400bbd76d30f7052ea992021-12-02T16:06:54ZXBP1-FoxO1 interaction regulates ER stress-induced autophagy in auditory cells10.1038/s41598-017-02960-12045-2322https://doaj.org/article/ce771875e796400bbd76d30f7052ea992017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02960-1https://doaj.org/toc/2045-2322Abstract 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.Akihiro KishinoKen HayashiChiaki HidaiTakeshi MasudaYasuyuki NomuraTakeshi OshimaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Akihiro Kishino Ken Hayashi Chiaki Hidai Takeshi Masuda Yasuyuki Nomura Takeshi Oshima XBP1-FoxO1 interaction regulates ER stress-induced autophagy in auditory cells
description	Abstract 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.
format	article
author	Akihiro Kishino Ken Hayashi Chiaki Hidai Takeshi Masuda Yasuyuki Nomura Takeshi Oshima
author_facet	Akihiro Kishino Ken Hayashi Chiaki Hidai Takeshi Masuda Yasuyuki Nomura Takeshi Oshima
author_sort	Akihiro Kishino
title	XBP1-FoxO1 interaction regulates ER stress-induced autophagy in auditory cells
title_short	XBP1-FoxO1 interaction regulates ER stress-induced autophagy in auditory cells
title_full	XBP1-FoxO1 interaction regulates ER stress-induced autophagy in auditory cells
title_fullStr	XBP1-FoxO1 interaction regulates ER stress-induced autophagy in auditory cells
title_full_unstemmed	XBP1-FoxO1 interaction regulates ER stress-induced autophagy in auditory cells
title_sort	xbp1-foxo1 interaction regulates er stress-induced autophagy in auditory cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/ce771875e796400bbd76d30f7052ea99
work_keys_str_mv	AT akihirokishino xbp1foxo1interactionregulateserstressinducedautophagyinauditorycells AT kenhayashi xbp1foxo1interactionregulateserstressinducedautophagyinauditorycells AT chiakihidai xbp1foxo1interactionregulateserstressinducedautophagyinauditorycells AT takeshimasuda xbp1foxo1interactionregulateserstressinducedautophagyinauditorycells AT yasuyukinomura xbp1foxo1interactionregulateserstressinducedautophagyinauditorycells AT takeshioshima xbp1foxo1interactionregulateserstressinducedautophagyinauditorycells
_version_	1718384806121701376

XBP1-FoxO1 interaction regulates ER stress-induced autophagy in auditory cells

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