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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| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
February 7, 2020
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| In: |
Proceedings of the National Academy of Sciences of the United States of America
Year: 2020, Volume: 117, Issue: 8, Pages: 4180-4187 |
| ISSN: | 1091-6490 |
| DOI: | 10.1073/pnas.1913481117 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1073/pnas.1913481117 Verlag, lizenzpflichtig, Volltext: https://www.pnas.org/content/117/8/4180 
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| Author Notes: | 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 |
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| 245 | 1 | 4 | |a The histone demethylase JMJD2B regulates endothelial-to-mesenchymal transition |c 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 |
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| 520 | |a 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. | ||
| 650 | 4 | |a EndMT | |
| 650 | 4 | |a epigenetics | |
| 650 | 4 | |a H3K9me3 | |
| 650 | 4 | |a JMJD2B | |
| 650 | 4 | |a SULF1 | |
| 700 | 1 | |a Heumüller, Andreas W. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Tombor, Lukas |e VerfasserIn |4 aut | |
| 700 | 1 | |a Hofmann, Patrick |e VerfasserIn |4 aut | |
| 700 | 1 | |a Muhly-Reinholz, Marion |e VerfasserIn |4 aut | |
| 700 | 1 | |a Fischer, Ariane |e VerfasserIn |4 aut | |
| 700 | 1 | |a Günther, Stefan |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kokot, Karoline E. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Hassel, David |e VerfasserIn |0 (DE-588)135801613 |0 (DE-627)693785608 |0 (DE-576)300653808 |4 aut | |
| 700 | 1 | |a Kumar, Sandeep |e VerfasserIn |4 aut | |
| 700 | 1 | |a Jo, Hanjoong |e VerfasserIn |4 aut | |
| 700 | 1 | |a Boon, Reinier A. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Abplanalp, Wesley |e VerfasserIn |4 aut | |
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| 700 | 1 | |a Boeckel, Jes-Niels |e VerfasserIn |4 aut | |
| 700 | 1 | |a Dimmeler, Stefanie |e VerfasserIn |4 aut | |
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| 787 | 0 | 8 | |i Errata |a Glaser, Simone F., 1991 - |t Correction: Glaser et al., The histone demethylase JMJD2B regulates endothelial-to-mesenchymal transition |d 2020 |w (DE-627)1744687242 |
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