The Transcription Factor IRF6 Co-Represses PPARγ-Mediated Cytoprotection in Ischemic Cerebrovascular Endothelial Cells

Abstract Activation of peroxisome proliferator-activated receptor gamma (PPARγ) in the cerebrovascular endothelium is a key suppressor of post-stroke brain damage. However, the role of PPARγ’s co-regulators during cerebral ischemia remains largely unknown. Here, we show that the transcription factor...

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Autores principales:	Rongzhong Huang, Zicheng Hu, Yuxing Feng, Lehua Yu, Xingsheng Li
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8cd52d0141c34d3ca60ee47ec36aaa90
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spelling	oai:doaj.org-article:8cd52d0141c34d3ca60ee47ec36aaa902021-12-02T11:52:17ZThe Transcription Factor IRF6 Co-Represses PPARγ-Mediated Cytoprotection in Ischemic Cerebrovascular Endothelial Cells10.1038/s41598-017-02095-32045-2322https://doaj.org/article/8cd52d0141c34d3ca60ee47ec36aaa902017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02095-3https://doaj.org/toc/2045-2322Abstract Activation of peroxisome proliferator-activated receptor gamma (PPARγ) in the cerebrovascular endothelium is a key suppressor of post-stroke brain damage. However, the role of PPARγ’s co-regulators during cerebral ischemia remains largely unknown. Here, we show that the transcription factor IRF6 is a novel PPARγ co-regulator that directly binds to and suppresses PPARγ activity in murine cerebrovascular endothelial cells. Moreover, IRF6 was also revealed to be a transcriptional target of PPARγ suppression, with PPARγ silencing significantly promoting IRF6 expression in cerebrovascular endothelial cells. In addition, IRF6 silencing significantly promoted pioglitazone’s cytoprotective effects in ischemic murine cerebrovascular endothelial cells. Mechanistically, IRF6 significantly suppressed PPARγ’s transcriptional inhibition of the ischemia-induced, pro-apoptotic microRNA miR-106a. In conclusion, we identified IRF6 as a novel PPARγ co-suppressor that serves a key role in suppressing PPARγ-mediated cerebrovascular endothelial cytoprotection following ischemia. Further investigation into IRF6 and other PPARγ co-regulators should provide additional insights into PPARγ’s cytoprotective role in the cerebrovascular endothelium following stroke.Rongzhong HuangZicheng HuYuxing FengLehua YuXingsheng LiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rongzhong Huang Zicheng Hu Yuxing Feng Lehua Yu Xingsheng Li The Transcription Factor IRF6 Co-Represses PPARγ-Mediated Cytoprotection in Ischemic Cerebrovascular Endothelial Cells
description	Abstract Activation of peroxisome proliferator-activated receptor gamma (PPARγ) in the cerebrovascular endothelium is a key suppressor of post-stroke brain damage. However, the role of PPARγ’s co-regulators during cerebral ischemia remains largely unknown. Here, we show that the transcription factor IRF6 is a novel PPARγ co-regulator that directly binds to and suppresses PPARγ activity in murine cerebrovascular endothelial cells. Moreover, IRF6 was also revealed to be a transcriptional target of PPARγ suppression, with PPARγ silencing significantly promoting IRF6 expression in cerebrovascular endothelial cells. In addition, IRF6 silencing significantly promoted pioglitazone’s cytoprotective effects in ischemic murine cerebrovascular endothelial cells. Mechanistically, IRF6 significantly suppressed PPARγ’s transcriptional inhibition of the ischemia-induced, pro-apoptotic microRNA miR-106a. In conclusion, we identified IRF6 as a novel PPARγ co-suppressor that serves a key role in suppressing PPARγ-mediated cerebrovascular endothelial cytoprotection following ischemia. Further investigation into IRF6 and other PPARγ co-regulators should provide additional insights into PPARγ’s cytoprotective role in the cerebrovascular endothelium following stroke.
format	article
author	Rongzhong Huang Zicheng Hu Yuxing Feng Lehua Yu Xingsheng Li
author_facet	Rongzhong Huang Zicheng Hu Yuxing Feng Lehua Yu Xingsheng Li
author_sort	Rongzhong Huang
title	The Transcription Factor IRF6 Co-Represses PPARγ-Mediated Cytoprotection in Ischemic Cerebrovascular Endothelial Cells
title_short	The Transcription Factor IRF6 Co-Represses PPARγ-Mediated Cytoprotection in Ischemic Cerebrovascular Endothelial Cells
title_full	The Transcription Factor IRF6 Co-Represses PPARγ-Mediated Cytoprotection in Ischemic Cerebrovascular Endothelial Cells
title_fullStr	The Transcription Factor IRF6 Co-Represses PPARγ-Mediated Cytoprotection in Ischemic Cerebrovascular Endothelial Cells
title_full_unstemmed	The Transcription Factor IRF6 Co-Represses PPARγ-Mediated Cytoprotection in Ischemic Cerebrovascular Endothelial Cells
title_sort	transcription factor irf6 co-represses pparγ-mediated cytoprotection in ischemic cerebrovascular endothelial cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/8cd52d0141c34d3ca60ee47ec36aaa90
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The Transcription Factor IRF6 Co-Represses PPARγ-Mediated Cytoprotection in Ischemic Cerebrovascular Endothelial Cells

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