The senotherapeutic drug ABT-737 disrupts aberrant p21 expression to restore liver regeneration in adult mice
| Autor: | Matej Durik, Umberto Di Vicino, William M. Keyes, Alba Mas, Elisa Pedone, Tania Knauer-Meyer, Birgit Ritschka, Hugues Jacobs, Maria Pia Cosma, Daniel Sampaio Gonçalves, Jean-Luc Plassat |
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| Přispěvatelé: | 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 de Strasbourg (UNISTRA), Centre for Genomic Regulation [Barcelona] (CRG), Universitat Pompeu Fabra [Barcelona] (UPF)-Centro Nacional de Analisis Genomico [Barcelona] (CNAG), Research Institute of Molecular Pathology (IMP), Universitat Pompeu Fabra [Barcelona] (UPF), ICREA Infection Biology Laboratory (Department of Experimental and Health Sciences), Work in the Keyes lab was funded in part by grants from the Spanish Ministry for Economy and Competitiveness (SAF2013-49082-P), La Fondation Recherche Medicale (FRM) (AJE20160635985), Fondation ARC (PJA20181208104), IDEX Attractivité-University of Strasbourg (IDEX2017), and La Fondation Schlumberger pour l’Education et la Recherche (FSER) (FSER 19-Year 2018). We acknowledge the support of the Spanish Ministry of Science and Innovation to the EMBL partnership, the Centro de Excelencia Severo Ochoa and the CERCA Programme/Generalitat de Catalunya., ANR-19-CE13-0023,SENAGE,La sénescence: une clef pour vieillir en bonne santé(2019), ANR-10-LABX-0030,INRT,Integrative Biology : Nuclear dynamics- Regenerative medicine - Translational medicine(2010), ANR-10-IDEX-0002,UNISTRA,Par-delà les frontières, l'Université de Strasbourg(2010), Keyes, Bill, La sénescence: une clef pour vieillir en bonne santé - - SENAGE2019 - ANR-19-CE13-0023 - AAPG2019 - VALID, Integrative Biology : Nuclear dynamics- Regenerative medicine - Translational medicine - - INRT2010 - ANR-10-LABX-0030 - LABX - VALID, Initiative d'excellence - Par-delà les frontières, l'Université de Strasbourg - - UNISTRA2010 - ANR-10-IDEX-0002 - IDEX - VALID |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
senescence [SDV]Life Sciences [q-bio] Piperazines senolytic Nitrophenols Mice 0302 clinical medicine Senilítics liver regeneration Fetge -- Regeneració Cells Cultured Cellular Senescence Regulation of gene expression Sulfonamides 0303 health sciences p16Ink4a p21 Liver regeneration Cell biology [SDV] Life Sciences [q-bio] Biphenyl compound medicine.anatomical_structure Liver 030220 oncology & carcinogenesis Hepatocyte Models Animal Female Cyclin-Dependent Kinase Inhibitor p21 Senescence Cell type [SDV.BC]Life Sciences [q-bio]/Cellular Biology Biology Cèl·lules hepàtiques 03 medical and health sciences Envelliment hepatocyte Genetics medicine Animals Regeneration Senolytic [SDV.BC] Life Sciences [q-bio]/Cellular Biology Cyclin-Dependent Kinase Inhibitor p16 030304 developmental biology ABT-737 Regeneration (biology) Biphenyl Compounds aging Mice Inbred C57BL Gene Expression Regulation Outlook Developmental Biology |
| Zdroj: | Genes and Development Genes and Development, 2020, 34 (7-8), pp.489-494. ⟨10.1101/gad.332643.119⟩ Genes Dev |
| ISSN: | 2013-4908 0890-9369 |
| DOI: | 10.1101/gad.332643.119⟩ |
| Popis: | Young mammals possess a limited regenerative capacity in some tissues, which is lost upon maturation. We investigated whether cellular senescence might play a role in such loss during liver regeneration. We found that following partial hepatectomy, the senescence-associated genes p21, p16Ink4a, and p19Arf become dynamically expressed in different cell types when regenerative capacity decreases, but without a full senescent response. However, we show that treatment with a senescence-inhibiting drug improves regeneration, by disrupting aberrantly prolonged p21 expression. This work suggests that senescence may initially develop from heterogeneous cellular responses, and that senotherapeutic drugs might be useful in promoting organ regeneration. Work in the Keyes lab was funded in part by grants from the Spanish Ministry for Economy and Competitiveness (SAF2013-49082-P), La Fondation Recherche Medicale (FRM) (AJE20160635985), Fondation ARC (PJA20181208104), IDEX Attractivité-University of Strasbourg (IDEX2017), and La Fondation Schlumberger pour l'Education et la Recherche (FSER) (FSER 19-Year 2018), and ANR (ANR-19-CE13-0023-03). Work was also supported by grant ANR-10-LABX-0030-INRT, a French State fund managed by the Agence Nationale de la Recherche under the frame program Investissements d'Avenir (ANR-10-IDEX-0002-02) |
| Databáze: | OpenAIRE |
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