Academic Journal
A non-canonical role of ELN protects from cellular senescence by limiting iron-dependent regulation of gene expression
| العنوان: | A non-canonical role of ELN protects from cellular senescence by limiting iron-dependent regulation of gene expression |
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| المؤلفون: | Czarnecka-Herok, Joanna, Zhu, Kexin, Flaman, Jean-Michel, Goehrig, Delphine, Vernier, Mathieu, Makulyte, Gabriela, Lamboux, Aline, Dragic, Helena, Rhinn, Muriel, Médard, Jean-Jacques, Faury, Gilles, Bertolino, Philippe, Balter, Vincent, Debret, Romain, Adnot, Serge, Martin, Nadine, Bernard, David |
| المساهمون: | Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard Lyon -Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard Lyon, Laboratoire de Géologie de Lyon - Terre, Planètes, Environnement (LGL-TPE), École normale supérieure de Lyon (ENS de Lyon), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut national des sciences de l'Univers (INSU - CNRS)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire CHU Grenoble (CHUGA), Hypoxie et PhysioPathologie (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique (LBTI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Hôpital Henri Mondor, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Justus-Liebig-Universität Gießen = Justus Liebig University (JLU), ANR-22-CE18-0040,TherAlveo,Approches biothérapeutiques à base d'élastine pour le traitement de l'emphysème pulmonaire(2022) |
| المصدر: | ISSN: 2213-2317 ; Redox Biology ; https://hal.science/hal-04631521 ; Redox Biology, 2024, 73, pp.103204. ⟨10.1016/j.redox.2024.103204⟩. |
| بيانات النشر: | HAL CCSD Elsevier |
| سنة النشر: | 2024 |
| المجموعة: | Université Jean Monnet – Saint-Etienne: HAL |
| مصطلحات موضوعية: | Cellular senescence, ELN, HMOX1, Iron, PHF8, ROS, [SDV]Life Sciences [q-bio] |
| الوصف: | International audience ; The ELN gene encodes tropoelastin which is used to generate elastic fibers that insure proper tissue elasticity. Decreased amounts of elastic fibers and/or accumulation of bioactive products of their cleavage, named elastokines, are thought to contribute to aging. Cellular senescence, characterized by a stable proliferation arrest and by the senescence-associated secretory phenotype (SASP), increases with aging, fostering the onset and progression of age-related diseases and overall aging, and has so far never been linked with elastin. Here, we identified that decrease in ELN either by siRNA in normal human fibroblasts or by knockout in mouse embryonic fibroblasts results in premature senescence. Surprisingly this effect is independent of elastic fiber degradation or elastokines production, but it relies on the rapid increase in HMOX1 after ELN downregulation. Moreover, the induction of HMOX1 depends on p53 and NRF2 transcription factors, and leads to an increase in iron, further mediating ELN downregulation-induced senescence. Screening of iron-dependent DNA and histones demethylases revealed a role for histone PHF8 demethylase in mediating ELN downregulation-induced senescence. Collectively, these results unveil a role for ELN in protecting cells from cellular senescence through a non-canonical mechanism involving a ROS/HMOX1/iron accumulation/PHF8 histone demethylase pathway reprogramming gene expression towards a senescence program. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/38810421; PUBMED: 38810421; PUBMEDCENTRAL: PMC11167390 |
| DOI: | 10.1016/j.redox.2024.103204 |
| الاتاحة: | https://hal.science/hal-04631521 https://hal.science/hal-04631521v1/document https://hal.science/hal-04631521v1/file/main.pdf https://doi.org/10.1016/j.redox.2024.103204 |
| Rights: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.3A954804 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.redox.2024.103204 |
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