Paraquat poisoning induced pulmonary epithelial mesenchymal transition through Notch1 pathway

Abstract Progressive pulmonary fibrosis is the most characteristic feature of subacute PQ poisoning. Epithelial-to-mesenchymal transition (EMT) is reported to be involved in the pulmonary fibrosis after PQ exposure. Recent evidence suggested Notch signaling is required for EMT. In this study, we inv...

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Autores principales:	Tiegang Li, Xiangming Yang, Shiyu Xin, Yan Cao, Nana Wang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2598cb6f943949089b4a0a49a8881f87
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spelling	oai:doaj.org-article:2598cb6f943949089b4a0a49a8881f872021-12-02T16:06:48ZParaquat poisoning induced pulmonary epithelial mesenchymal transition through Notch1 pathway10.1038/s41598-017-01069-92045-2322https://doaj.org/article/2598cb6f943949089b4a0a49a8881f872017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01069-9https://doaj.org/toc/2045-2322Abstract Progressive pulmonary fibrosis is the most characteristic feature of subacute PQ poisoning. Epithelial-to-mesenchymal transition (EMT) is reported to be involved in the pulmonary fibrosis after PQ exposure. Recent evidence suggested Notch signaling is required for EMT. In this study, we investigated whether Notch1 and TGF-β1/Smad3 signaling was involved in EMT caused by PQ. It is demonstrated that A549 cells underwent EMT after treated with PQ at dose of 300 μmol/L for 6 days, charactered by increasing expression of mesenchymal marker α-SMA and decreasing expression of epithelial marker E-cadherin. We found that there was an apparent increased expression of Notch1 and jagged-1 in PQ induced EMT process. EMT could be enhanced by Jagged-1 ligand of Notch1, and be blocked by DAPT, a γ-secretase inhibitor. Our data also showed that the expression of TGF-β1/Smad3 increased after Notch1 is elevated in EMT caused by PQ. Jagged-1 significantly induced SMA expression, and this induction was completely inhibited by SB431542 in A549 cells. In conclusion, we demonstrated that Notch1 pathway was important in EMT induced by PQ, and TGF-β1/Smad3 signaling partly plays a role as the downstream of Notch1.Tiegang LiXiangming YangShiyu XinYan CaoNana WangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tiegang Li Xiangming Yang Shiyu Xin Yan Cao Nana Wang Paraquat poisoning induced pulmonary epithelial mesenchymal transition through Notch1 pathway
description	Abstract Progressive pulmonary fibrosis is the most characteristic feature of subacute PQ poisoning. Epithelial-to-mesenchymal transition (EMT) is reported to be involved in the pulmonary fibrosis after PQ exposure. Recent evidence suggested Notch signaling is required for EMT. In this study, we investigated whether Notch1 and TGF-β1/Smad3 signaling was involved in EMT caused by PQ. It is demonstrated that A549 cells underwent EMT after treated with PQ at dose of 300 μmol/L for 6 days, charactered by increasing expression of mesenchymal marker α-SMA and decreasing expression of epithelial marker E-cadherin. We found that there was an apparent increased expression of Notch1 and jagged-1 in PQ induced EMT process. EMT could be enhanced by Jagged-1 ligand of Notch1, and be blocked by DAPT, a γ-secretase inhibitor. Our data also showed that the expression of TGF-β1/Smad3 increased after Notch1 is elevated in EMT caused by PQ. Jagged-1 significantly induced SMA expression, and this induction was completely inhibited by SB431542 in A549 cells. In conclusion, we demonstrated that Notch1 pathway was important in EMT induced by PQ, and TGF-β1/Smad3 signaling partly plays a role as the downstream of Notch1.
format	article
author	Tiegang Li Xiangming Yang Shiyu Xin Yan Cao Nana Wang
author_facet	Tiegang Li Xiangming Yang Shiyu Xin Yan Cao Nana Wang
author_sort	Tiegang Li
title	Paraquat poisoning induced pulmonary epithelial mesenchymal transition through Notch1 pathway
title_short	Paraquat poisoning induced pulmonary epithelial mesenchymal transition through Notch1 pathway
title_full	Paraquat poisoning induced pulmonary epithelial mesenchymal transition through Notch1 pathway
title_fullStr	Paraquat poisoning induced pulmonary epithelial mesenchymal transition through Notch1 pathway
title_full_unstemmed	Paraquat poisoning induced pulmonary epithelial mesenchymal transition through Notch1 pathway
title_sort	paraquat poisoning induced pulmonary epithelial mesenchymal transition through notch1 pathway
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/2598cb6f943949089b4a0a49a8881f87
work_keys_str_mv	AT tiegangli paraquatpoisoninginducedpulmonaryepithelialmesenchymaltransitionthroughnotch1pathway AT xiangmingyang paraquatpoisoninginducedpulmonaryepithelialmesenchymaltransitionthroughnotch1pathway AT shiyuxin paraquatpoisoninginducedpulmonaryepithelialmesenchymaltransitionthroughnotch1pathway AT yancao paraquatpoisoninginducedpulmonaryepithelialmesenchymaltransitionthroughnotch1pathway AT nanawang paraquatpoisoninginducedpulmonaryepithelialmesenchymaltransitionthroughnotch1pathway
_version_	1718384830275649536

Paraquat poisoning induced pulmonary epithelial mesenchymal transition through Notch1 pathway

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