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

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...

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Detalles Bibliográficos
Autores: Ritschka, Birgit, 1985-, Knauer-Meyer, Tania, Sampaio Gonçalves, Daniel, Mas, Alba, Plassat, Jean-Luc, Durik, Matej, Jacobs, Hugues, Pedone, Elisa, 1985-, Di Vicino, Umberto, Cosma, Maria Pia, 1970-, Keyes, William M., 1973-
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/44600
Acceso en línea:http://hdl.handle.net/10230/44600
http://dx.doi.org/10.1101/gad.332643.119
Access Level:acceso abierto
Palabra clave:Fetge -- Regeneració
Cèl·lules hepàtiques
Envelliment
Senilítics
Descripción
Sumario: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.