| First Author | Leerach N | Year | 2021 |
| Journal | Biochem Biophys Res Commun | Volume | 555 |
| Pages | 74-80 | PubMed ID | 33813279 |
| Mgi Jnum | J:305607 | Mgi Id | MGI:6706070 |
| Doi | 10.1016/j.bbrc.2021.03.139 | Citation | Leerach N, et al. (2021) RAGE signaling antagonist suppresses mouse macrophage foam cell formation. Biochem Biophys Res Commun 555:74-80 |
| abstractText | 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-kappaB 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. |
