The histone demethylase JMJD2B regulates endothelial-to-mesenchymal transition

• Verfasst von: Glaser, Simone F. [VerfasserIn]
• Verfasst von: Heumüller, Andreas W. [VerfasserIn]
• Verfasst von: Tombor, Lukas [VerfasserIn]
• Verfasst von: Hofmann, Patrick [VerfasserIn]
• Verfasst von: Muhly-Reinholz, Marion [VerfasserIn]
• Verfasst von: Fischer, Ariane [VerfasserIn]
• Verfasst von: Günther, Stefan [VerfasserIn]
• Verfasst von: Kokot, Karoline E. [VerfasserIn]
• Verfasst von: Hassel, David [VerfasserIn]
• Verfasst von: Kumar, Sandeep [VerfasserIn]
• Verfasst von: Jo, Hanjoong [VerfasserIn]
• Verfasst von: Boon, Reinier A. [VerfasserIn]
• Verfasst von: Abplanalp, Wesley [VerfasserIn]
• Verfasst von: John, David [VerfasserIn]
• Verfasst von: Boeckel, Jes-Niels [VerfasserIn]
• Verfasst von: Dimmeler, Stefanie [VerfasserIn]
• Titel: The histone demethylase JMJD2B regulates endothelial-to-mesenchymal transition
• Verf.angabe: 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
• E-Jahr: 2020
• Jahr: February 7, 2020
• Umfang: 8 S.
• Fussnoten: Gesehen am 06.04.2020
• Titel Quelle: Enthalten in: National Academy of Sciences (Washington, DC)Proceedings of the National Academy of Sciences of the United States of America
• Ort Quelle: Washington, DC : National Acad. of Sciences, 1915
• Jahr Quelle: 2020
• Band/Heft Quelle: 117(2020), 8, Seite 4180-4187
• ISSN Quelle: 1091-6490
• DOI: doi:10.1073/pnas.1913481117
• Datenträger: Online-Ressource
• Sprache: eng
• Bibliogr. Hinweis: Errata: Glaser, Simone F., 1991 - : Correction: Glaser et al., The histone demethylase JMJD2B regulates endothelial-to-mesenchymal transition
• Sach-SW: EndMT
• Sach-SW: epigenetics
• Sach-SW: H3K9me3
• Sach-SW: JMJD2B
• Sach-SW: SULF1
• K10plus-PPN: 1694089614

Abstract

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.