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The histone demethylase JMJD2B regulates endothelial-to-mesenchymal transition.
Glaser, Simone F; Heumüller, Andreas W; Tombor, Lukas; Hofmann, Patrick; Muhly-Reinholz, Marion; Fischer, Ariane; Günther, Stefan; Kokot, Karoline E; Hassel, David; Kumar, Sandeep; Jo, Hanjoong; Boon, Reinier A; Abplanalp, Wesley; John, David; Boeckel, Jes-Niels; Dimmeler, Stefanie.
Afiliación
  • Glaser SF; Institute for Cardiovascular Regeneration, Goethe University, 60590 Frankfurt, Germany.
  • Heumüller AW; German Center of Cardiovascular Research (DZHK), Partner Site Rhine/Main 60439 Frankfurt, Germany.
  • Tombor L; Faculty for Biological Sciences, Goethe University, 60590 Frankfurt, Germany.
  • Hofmann P; Institute for Cardiovascular Regeneration, Goethe University, 60590 Frankfurt, Germany.
  • Muhly-Reinholz M; German Center of Cardiovascular Research (DZHK), Partner Site Rhine/Main 60439 Frankfurt, Germany.
  • Fischer A; Faculty for Biological Sciences, Goethe University, 60590 Frankfurt, Germany.
  • Günther S; Institute for Cardiovascular Regeneration, Goethe University, 60590 Frankfurt, Germany.
  • Kokot KE; German Center of Cardiovascular Research (DZHK), Partner Site Rhine/Main 60439 Frankfurt, Germany.
  • Hassel D; Institute for Cardiovascular Regeneration, Goethe University, 60590 Frankfurt, Germany.
  • Kumar S; German Center of Cardiovascular Research (DZHK), Partner Site Rhine/Main 60439 Frankfurt, Germany.
  • Jo H; Institute for Cardiovascular Regeneration, Goethe University, 60590 Frankfurt, Germany.
  • Boon RA; Institute for Cardiovascular Regeneration, Goethe University, 60590 Frankfurt, Germany.
  • Abplanalp W; DZHK, Partner Site Rhine/Main 61231 Bad Nauheim, Germany.
  • John D; Cardiopulmonary Institute (CPI), Bioinformatics and Deep Sequencing Platform, Dept. I, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.
  • Boeckel JN; Klinik und Poliklinik für Kardiologie, Universitätsklinikum Leipzig, 04103 Leipzig, Germany.
  • Dimmeler S; DZHK, Heidelberg/Mannheim 69120 Heidelberg, Germany.
Proc Natl Acad Sci U S A ; 117(8): 4180-4187, 2020 02 25.
Article en En | MEDLINE | ID: mdl-32034099
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-ß2-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-ß 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.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Células Endoteliales / Histona Demetilasas con Dominio de Jumonji / Transición Epitelial-Mesenquimal / Células Madre Mesenquimatosas Límite: Humans Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2020 Tipo del documento: Article País de afiliación: Alemania

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Células Endoteliales / Histona Demetilasas con Dominio de Jumonji / Transición Epitelial-Mesenquimal / Células Madre Mesenquimatosas Límite: Humans Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2020 Tipo del documento: Article País de afiliación: Alemania