RAGE signaling antagonist suppresses mouse macrophage foam cell formation
RAGE signaling antagonist suppresses mouse macrophage foam cell formation
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DOI：
10.1016/j.bbrc.2021.03.139
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发表时间：
2021-04-01
影响因子：
3.1
通讯作者：
Yamamoto, Yasuhiko
中科院分区：
文献类型：
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作者：
Leerach, Nontaphat;Munesue, Seiichi;Yamamoto, Yasuhiko
晚期糖基化终产物受体（AGEs受体，RECEPTOR）与多种配体的结合可引起慢性血管炎症，如动脉粥样硬化。已知胞质尾区信号转导蛋白（ctR）与透明相关的信号转导蛋白1（Diaph 1）的结合产生非透明的细胞内信号转导和随后的细胞应答。然而，ctl/Diaph 1相互作用的抑制剂在减弱动脉粥样硬化发展中的有效性尚不清楚。在这项研究中，使用来自Ager（+/+）和Ager（-/-）小鼠的巨噬细胞，我们验证了抑制剂对AGEs-β诱导的泡沫细胞形成的影响。抑制剂显着抑制AGEs-β-诱发的Rac 1活性，细胞侵袭，氧化低密度脂蛋白的摄取，以及AGEs诱导的NF-κ B激活和促炎基因表达上调。此外，IL-10，抗炎基因的表达，恢复这种拮抗剂。这些发现表明，RAGE-Diaph 1抑制剂可能是一种潜在的治疗药物，用于治疗RAGE相关疾病，如慢性炎症和动脉粥样硬化。(C)2021年由Elsevier Inc.出版
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-kB 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. (C) 2021 Published by Elsevier Inc.