RAGE signaling antagonist suppresses mouse macrophage foam cell formation.
Biochem Biophys Res Commun
; 555: 74-80, 2021 05 28.
Article
em En
| MEDLINE
| ID: mdl-33813279
ABSTRACT
The engagement of the receptor for advanced glycation end-products (receptor for AGEs, RAGE) with diverse ligands could elicit chronic vascular inflammation, such as atherosclerosis. Binding of cytoplasmic tail RAGE (ctRAGE) to diaphanous-related formin 1 (Diaph1) is known to yield RAGE intracellular signal transduction and subsequent cellular responses. However, the effectiveness of an inhibitor of the ctRAGE/Diaph1 interaction in attenuating the development of atherosclerosis is unclear. In this study, using macrophages from Ager+/+ and Ager-/- mice, we validated the effects of an inhibitor on AGEs-RAGE-induced foam cell formation. The inhibitor significantly suppressed AGEs-RAGE-evoked Rac1 activity, cell invasion, and uptake of oxidized low-density lipoprotein, as well as AGEs-induced NF-κB activation and upregulation of proinflammatory gene expression. Moreover, expression of Il-10, an anti-inflammatory gene, was restored by this antagonist. These findings suggest that the RAGE-Diaph1 inhibitor could be a potential therapeutic drug against RAGE-related diseases, such as chronic inflammation and atherosclerosis.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Macrófagos Peritoneais
/
Receptor para Produtos Finais de Glicação Avançada
/
Células Espumosas
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article