دورية أكاديمية

egr3 is a mechanosensitive transcription factor gene required for cardiac valve morphogenesis.

التفاصيل البيبلوغرافية
العنوان: egr3 is a mechanosensitive transcription factor gene required for cardiac valve morphogenesis.
المؤلفون: da Silva AR; Max Planck Institute for Heart and Lung Research, Department of Developmental Genetics, Bad Nauheim, Germany.; German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Bad Nauheim, Germany.; Cardio-Pulmonary Institute (CPI), Bad Nauheim, Germany., Gunawan F; Max Planck Institute for Heart and Lung Research, Department of Developmental Genetics, Bad Nauheim, Germany.; German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Bad Nauheim, Germany.; Cardio-Pulmonary Institute (CPI), Bad Nauheim, Germany., Boezio GLM; Max Planck Institute for Heart and Lung Research, Department of Developmental Genetics, Bad Nauheim, Germany.; German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Bad Nauheim, Germany.; Cardio-Pulmonary Institute (CPI), Bad Nauheim, Germany., Faure E; Aix Marseille Université, INSERM, MMG, U1251, 13005 Marseille, France., Théron A; Aix Marseille Université, INSERM, MMG, U1251, 13005 Marseille, France.; Service de Chirurgie Cardiaque, AP-HM, Hôpital de la Timone, 13005 Marseille, France., Avierinos JF; Aix Marseille Université, INSERM, MMG, U1251, 13005 Marseille, France.; Service de Cardiologie, AP-HM, Hôpital de la Timone, 13005 Marseille, France., Lim S; Max Planck Institute for Heart and Lung Research, Department of Developmental Genetics, Bad Nauheim, Germany., Jha SG; Max Planck Institute for Heart and Lung Research, Department of Developmental Genetics, Bad Nauheim, Germany., Ramadass R; Max Planck Institute for Heart and Lung Research, Department of Developmental Genetics, Bad Nauheim, Germany., Guenther S; German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Bad Nauheim, Germany.; Cardio-Pulmonary Institute (CPI), Bad Nauheim, Germany.; Bioinformatics and Deep Sequencing Platform, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany., Looso M; German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Bad Nauheim, Germany.; Cardio-Pulmonary Institute (CPI), Bad Nauheim, Germany.; Bioinformatics Core Unit (BCU), Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany., Zaffran S; Aix Marseille Université, INSERM, MMG, U1251, 13005 Marseille, France., Juan T; Max Planck Institute for Heart and Lung Research, Department of Developmental Genetics, Bad Nauheim, Germany.; German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Bad Nauheim, Germany.; Cardio-Pulmonary Institute (CPI), Bad Nauheim, Germany., Stainier DYR; Max Planck Institute for Heart and Lung Research, Department of Developmental Genetics, Bad Nauheim, Germany.; German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Bad Nauheim, Germany.; Cardio-Pulmonary Institute (CPI), Bad Nauheim, Germany.
المصدر: Science advances [Sci Adv] 2024 May 17; Vol. 10 (20), pp. eadl0633. Date of Electronic Publication: 2024 May 15.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101653440 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2375-2548 (Electronic) Linking ISSN: 23752548 NLM ISO Abbreviation: Sci Adv Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : American Association for the Advancement of Science, [2015]-
مواضيع طبية MeSH: Zebrafish* , Heart Valves*/metabolism , Heart Valves*/embryology , Zebrafish Proteins*/genetics , Zebrafish Proteins*/metabolism , Morphogenesis*/genetics , Early Growth Response Protein 3*/metabolism , Early Growth Response Protein 3*/genetics, Animals ; Humans ; Gene Expression Regulation, Developmental ; Endothelial Cells/metabolism ; Mechanotransduction, Cellular ; Swine
مستخلص: Biomechanical forces, and their molecular transducers, including key mechanosensitive transcription factor genes, such as KLF2 , are required for cardiac valve morphogenesis. However, klf2 mutants fail to completely recapitulate the valveless phenotype observed under no-flow conditions. Here, we identify the transcription factor EGR3 as a conserved biomechanical force transducer critical for cardiac valve formation. We first show that egr3 null zebrafish display a complete and highly penetrant loss of valve leaflets, leading to severe blood regurgitation. Using tissue-specific loss- and gain-of-function tools, we find that during cardiac valve formation, Egr3 functions cell-autonomously in endothelial cells, and identify one of its effectors, the nuclear receptor Nr4a2b. We further find that mechanical forces up-regulate egr3 / EGR3 expression in the developing zebrafish heart and in porcine valvular endothelial cells, as well as during human aortic valve remodeling. Altogether, these findings reveal that EGR3 is necessary to transduce the biomechanical cues required for zebrafish cardiac valve morphogenesis, and potentially for pathological aortic valve remodeling in humans.
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تواريخ الأحداث: Date Created: 20240515 Date Completed: 20240515 Latest Revision: 20240801
رمز التحديث: 20240801
مُعرف محوري في PubMed: PMC11095463
DOI: 10.1126/sciadv.adl0633
PMID: 38748804
قاعدة البيانات: MEDLINE
الوصف
تدمد:2375-2548
DOI:10.1126/sciadv.adl0633