ROS-Nrf2 pathway mediates the development of TGF-β1-induced epithelial-mesenchymal transition through the activation of Notch signaling

Epithelial-mesenchymal transition (EMT) is a cellular process by which epithelial cells transform to acquire mesenchymal phenotypes. Accumulating evidence indicate the involvement of EMT in the progression of malignant diseases. Notch signaling mediates TGF-β1-induced EMT through direct transcriptio...

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Autores principales:	Kai Yazaki, Yosuke Matsuno, Kazufumi Yoshida, Mingma Sherpa, Masayuki Nakajima, Masashi Matsuyama, Takumi Kiwamoto, Yuko Morishima, Yukio Ishii, Nobuyuki Hizawa
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	EMT TGF-β1 Notch signaling ROS Nrf2 A549 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/27e2a1627e994865be7e7a4df59a56d5
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spelling	oai:doaj.org-article:27e2a1627e994865be7e7a4df59a56d52021-11-10T04:17:26ZROS-Nrf2 pathway mediates the development of TGF-β1-induced epithelial-mesenchymal transition through the activation of Notch signaling0171-933510.1016/j.ejcb.2021.151181https://doaj.org/article/27e2a1627e994865be7e7a4df59a56d52021-09-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0171933521000327https://doaj.org/toc/0171-9335Epithelial-mesenchymal transition (EMT) is a cellular process by which epithelial cells transform to acquire mesenchymal phenotypes. Accumulating evidence indicate the involvement of EMT in the progression of malignant diseases. Notch signaling mediates TGF-β1-induced EMT through direct transcriptional activation of Snai1. The molecular mechanism how TGF-β1 activates Notch signaling, however, remains unknown. In this study, we show a pivotal role for reactive oxygen species (ROS)-Nrf2 pathway in TGF-β1-induced Notch signaling activation and EMT development. TGF-β1 induces Nrf2 activation through ROS production. Inhibiting Nrf2 activation either by reducing ROS levels by N-acetylcysteine or by knocking down of Nrf2 by small interfering RNA attenuated both Notch signaling activation and EMT development. TGF-β1 induced the transcription of Notch4 via Nrf2-dependent promoter activation. In conclusion, our study indicates the ROS-Nrf2 pathway mediates the development of TGF-β1-induced EMT through the activation of Notch signaling.Kai YazakiYosuke MatsunoKazufumi YoshidaMingma SherpaMasayuki NakajimaMasashi MatsuyamaTakumi KiwamotoYuko MorishimaYukio IshiiNobuyuki HizawaElsevierarticleEMTTGF-β1Notch signalingROSNrf2A549CytologyQH573-671ENEuropean Journal of Cell Biology, Vol 100, Iss 7, Pp 151181- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	EMT TGF-β1 Notch signaling ROS Nrf2 A549 Cytology QH573-671
spellingShingle	EMT TGF-β1 Notch signaling ROS Nrf2 A549 Cytology QH573-671 Kai Yazaki Yosuke Matsuno Kazufumi Yoshida Mingma Sherpa Masayuki Nakajima Masashi Matsuyama Takumi Kiwamoto Yuko Morishima Yukio Ishii Nobuyuki Hizawa ROS-Nrf2 pathway mediates the development of TGF-β1-induced epithelial-mesenchymal transition through the activation of Notch signaling
description	Epithelial-mesenchymal transition (EMT) is a cellular process by which epithelial cells transform to acquire mesenchymal phenotypes. Accumulating evidence indicate the involvement of EMT in the progression of malignant diseases. Notch signaling mediates TGF-β1-induced EMT through direct transcriptional activation of Snai1. The molecular mechanism how TGF-β1 activates Notch signaling, however, remains unknown. In this study, we show a pivotal role for reactive oxygen species (ROS)-Nrf2 pathway in TGF-β1-induced Notch signaling activation and EMT development. TGF-β1 induces Nrf2 activation through ROS production. Inhibiting Nrf2 activation either by reducing ROS levels by N-acetylcysteine or by knocking down of Nrf2 by small interfering RNA attenuated both Notch signaling activation and EMT development. TGF-β1 induced the transcription of Notch4 via Nrf2-dependent promoter activation. In conclusion, our study indicates the ROS-Nrf2 pathway mediates the development of TGF-β1-induced EMT through the activation of Notch signaling.
format	article
author	Kai Yazaki Yosuke Matsuno Kazufumi Yoshida Mingma Sherpa Masayuki Nakajima Masashi Matsuyama Takumi Kiwamoto Yuko Morishima Yukio Ishii Nobuyuki Hizawa
author_facet	Kai Yazaki Yosuke Matsuno Kazufumi Yoshida Mingma Sherpa Masayuki Nakajima Masashi Matsuyama Takumi Kiwamoto Yuko Morishima Yukio Ishii Nobuyuki Hizawa
author_sort	Kai Yazaki
title	ROS-Nrf2 pathway mediates the development of TGF-β1-induced epithelial-mesenchymal transition through the activation of Notch signaling
title_short	ROS-Nrf2 pathway mediates the development of TGF-β1-induced epithelial-mesenchymal transition through the activation of Notch signaling
title_full	ROS-Nrf2 pathway mediates the development of TGF-β1-induced epithelial-mesenchymal transition through the activation of Notch signaling
title_fullStr	ROS-Nrf2 pathway mediates the development of TGF-β1-induced epithelial-mesenchymal transition through the activation of Notch signaling
title_full_unstemmed	ROS-Nrf2 pathway mediates the development of TGF-β1-induced epithelial-mesenchymal transition through the activation of Notch signaling
title_sort	ros-nrf2 pathway mediates the development of tgf-β1-induced epithelial-mesenchymal transition through the activation of notch signaling
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/27e2a1627e994865be7e7a4df59a56d5
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ROS-Nrf2 pathway mediates the development of TGF-β1-induced epithelial-mesenchymal transition through the activation of Notch signaling

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