1. RAGE signaling antagonist suppresses mouse macrophage foam cell formation.
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Leerach, Nontaphat, Munesue, Seiichi, Harashima, Ai, Kimura, Kumi, Oshima, Yu, Kawano, Shuhei, Tanaka, Mariko, Niimura, Akane, Sakulsak, Natthiya, Yamamoto, Hiroshi, Hori, Osamu, and Yamamoto, Yasuhiko
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RECEPTOR for advanced glycation end products (RAGE) , *ADVANCED glycation end-products , *CELLULAR signal transduction , *MACROPHAGES , *FOAM cells , *MICE - 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. • The ctRAGE/Diaph1 inhibitor (inhRAGE) blocked AGEs-induced Rac1 phosphorylation. • The inhRAGE also inhibited AGEs-RAGE-mediated NF-κB activation. • The treatment of inhRAGE suppressed macrophage invasion, lipid engulfment and inflammation. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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