Suppression of TREX1 deficiency-induced cellular senescence and interferonopathies by inhibition of DNA damage response.
iScience
; 26(7): 107090, 2023 Jul 21.
Article
en En
| MEDLINE
| ID: mdl-37416470
ABSTRACT
TREX1 encodes a major DNA exonuclease and mutations of this gene are associated with type I interferonopathies in human. Mice with Trex1 deletion or mutation have shortened life spans accompanied by a senescence-associated secretory phenotype. However, the contribution of cellular senescence in TREX1 deficiency-induced type I interferonopathies remains unknown. We found that features of cellular senescence present in Trex1-/- mice are induced by multiple factors, particularly DNA damage. The cGAS-STING and DNA damage response pathways are required for maintaining TREX1 deletion-induced cellular senescence. Inhibition of the DNA damage response, such as with Checkpoint kinase 2 (CHK2) inhibitor, partially alleviated progression of type I interferonopathies and lupus-like features in the mice. These data provide insights into the initiation and development of type I interferonopathies and lupus-like diseases, and may help inform the development of targeted therapeutics.
Texto completo:
1
Banco de datos:
MEDLINE
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
IScience
Año:
2023
Tipo del documento:
Article
País de afiliación:
China