Diabetes Research Program, Department of Medicine, New York University Grossman School of Medicine, New York, NY 10016, USA.
Department of Chemistry, The State University of New York at Albany, Albany, NY 12222, USA.
Int J Mol Sci. 2022 Apr 21;23(9):4579. doi: 10.3390/ijms23094579.
Increasing evidence links the RAGE (receptor for advanced glycation end products)/DIAPH1 (Diaphanous 1) signaling axis to the pathogenesis of diabetic complications. RAGE is a multi-ligand receptor and through these ligand-receptor interactions, extensive maladaptive effects are exerted on cell types and tissues targeted for dysfunction in hyperglycemia observed in both type 1 and type 2 diabetes. Recent evidence indicates that RAGE ligands, acting as damage-associated molecular patterns molecules, or DAMPs, through RAGE may impact interferon signaling pathways, specifically through upregulation of IRF7 (interferon regulatory factor 7), thereby heralding and evoking pro-inflammatory effects on vulnerable tissues. Although successful targeting of RAGE in the clinical milieu has, to date, not been met with success, recent approaches to target RAGE intracellular signaling may hold promise to fill this critical gap. This review focuses on recent examples of highlights and updates to the pathobiology of RAGE and DIAPH1 in diabetic complications.
越来越多的证据表明，RAGE（晚期糖基化终产物受体）/DIAPH1（盘状结构域 1）信号轴与糖尿病并发症的发病机制有关。RAGE 是一种多配体受体，通过这些配体-受体相互作用，对细胞类型和组织产生广泛的适应性不良影响，这些细胞类型和组织在 1 型和 2 型糖尿病中均观察到高血糖导致的功能障碍。最近的证据表明，RAGE 配体作为损伤相关分子模式分子，或 DAMPs，通过 RAGE 可能影响干扰素信号通路，特别是通过上调 IRF7（干扰素调节因子 7），从而对脆弱组织产生炎症前效应。尽管迄今为止，在临床环境中成功靶向 RAGE 尚未取得成功，但最近靶向 RAGE 细胞内信号的方法可能有希望填补这一关键空白。本综述重点介绍了 RAGE 和 DIAPH1 在糖尿病并发症中的病理生物学的最新亮点和更新。
