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...

ver descrição completa

Detalhes 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-
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/44600
Acesso em linha:http://hdl.handle.net/10230/44600
http://dx.doi.org/10.1101/gad.332643.119
Access Level:acceso abierto
Palavra-chave:Fetge -- Regeneració
Cèl·lules hepàtiques
Envelliment
Senilítics
Descrição
Resumo: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.