The senotherapeutic drug ABT-737 disrupts aberrant p21 expression to restore liver regeneration in adult mice

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Abstract
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.
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Funding Information
  • Spanish Ministry for Economy and Competitiveness (SAF2013-49082-P)
  • La Fondation Recherche Medicale (AJE20160635985)
  • Fondation ARC (PJA20181208104)
  • IDEX Attractivité-University of Strasbourg (IDEX2017)
  • La Fondation Schlumberger pour l'Education et la Recherche (FSER 19-Year 2018)
  • ANR (ANR-19-CE13-0023-03, ANR-10-LABX-0030-INRT)
  • Agence Nationale de la Recherche (ANR-10-IDEX-0002-02)

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