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The histone demethylase JMJD2B regulates endothelial-to-mesenchymal transition

Endothelial cells play an important role in maintenance of the vascular system and the repair after injury. Under proinflammatory conditions, endothelial cells can acquire a mesenchymal phenotype by a process named endothelial-to-mesenchymal transition (EndMT), which affects the functional propertie...

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Hauptverfasser: Glaser, Simone F. (VerfasserIn) , Heumüller, Andreas W. (VerfasserIn) , Tombor, Lukas (VerfasserIn) , Hofmann, Patrick (VerfasserIn) , Muhly-Reinholz, Marion (VerfasserIn) , Fischer, Ariane (VerfasserIn) , Günther, Stefan (VerfasserIn) , Kokot, Karoline E. (VerfasserIn) , Hassel, David (VerfasserIn) , Kumar, Sandeep (VerfasserIn) , Jo, Hanjoong (VerfasserIn) , Boon, Reinier A. (VerfasserIn) , Abplanalp, Wesley (VerfasserIn) , John, David (VerfasserIn) , Boeckel, Jes-Niels (VerfasserIn) , Dimmeler, Stefanie (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: February 7, 2020
In: Proceedings of the National Academy of Sciences of the United States of America
Year: 2020, Jahrgang: 117, Heft: 8, Pages: 4180-4187
ISSN:1091-6490
DOI:10.1073/pnas.1913481117
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1073/pnas.1913481117
Verlag, lizenzpflichtig, Volltext: https://www.pnas.org/content/117/8/4180
Volltext
Verfasserangaben:Simone F. Glaser, Andreas W. Heumüller, Lukas Tombor, Patrick Hofmann, Marion Muhly-Reinholz, Ariane Fischer, Stefan Günther, Karoline E. Kokot, David Hassel, Sandeep Kumar, Hanjoong Jo, Reinier A. Boon, Wesley Abplanalp, David John, Jes-Niels Boeckel, and Stefanie Dimmeler
Beschreibung
Zusammenfassung:Endothelial cells play an important role in maintenance of the vascular system and the repair after injury. Under proinflammatory conditions, endothelial cells can acquire a mesenchymal phenotype by a process named endothelial-to-mesenchymal transition (EndMT), which affects the functional properties of endothelial cells. Here, we investigated the epigenetic control of EndMT. We show that the histone demethylase JMJD2B is induced by EndMT-promoting, proinflammatory, and hypoxic conditions. Silencing of JMJD2B reduced TGF-β2-induced expression of mesenchymal genes, prevented the alterations in endothelial morphology and impaired endothelial barrier function. Endothelial-specific deletion of JMJD2B in vivo confirmed a reduction of EndMT after myocardial infarction. EndMT did not affect global H3K9me3 levels but induced a site-specific reduction of repressive H3K9me3 marks at promoters of mesenchymal genes, such as Calponin (CNN1), and genes involved in TGF-β signaling, such as AKT Serine/Threonine Kinase 3 (AKT3) and Sulfatase 1 (SULF1). Silencing of JMJD2B prevented the EndMT-induced reduction of H3K9me3 marks at these promotors and further repressed these EndMT-related genes. Our study reveals that endothelial identity and function is critically controlled by the histone demethylase JMJD2B, which is induced by EndMT-promoting, proinflammatory, and hypoxic conditions, and supports the acquirement of a mesenchymal phenotype.
Beschreibung:Gesehen am 06.04.2020
Beschreibung:Online Resource
ISSN:1091-6490
DOI:10.1073/pnas.1913481117

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