Son Myeongjoo, Chung Wook-Jin, Oh Seyeon, Ahn Hyosang, Choi Chang Hu, Hong Suntaek, Park Kook Yang, Son Kuk Hui, Byun Kyunghee
Department of Anatomy and Cell Biology, Graduate School of Medicine, Gachon University, Incheon, 21936 Republic of Korea.
Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, 21999 Republic of Korea.
Immun Ageing. 2017 Jun 5;14:12. doi: 10.1186/s12979-017-0095-2. eCollection 2017.
Much evidence indicates receptor for advanced glycation end products (RAGE) related inflammation play essential roles during aging. However, the majority of studies have focused on advanced glycation end products (AGEs) and not on other RAGE ligands. In the present study, the authors evaluated whether the accumulation of RAGE ligands and binding intensities between RAGE and its ligands differ in kidney, liver, and skeletal muscle during aging.
In C57BL/6 N mice aged 12 weeks, 12 months, and 22 months, ligands accumulation, binding intensities between RAGE and its ligands, activated macrophage infiltration, M1/M2 macrophage expression, glyoxalase-1expression, and signal pathways related to inflammation were evaluated. The RAGE ligands age-associated accumulation patterns were found to be organ dependent. Binding intensities between RAGE and its ligands in kidney and liver increased with age, but those in skeletal muscle were unchanged. Infiltration of activated macrophages in kidney and liver increased with age, but infiltration in the skeletal muscle was unchanged. M1 expression increased and M2 and glyoxalase-1 expression decreased with age in kidney and liver, but their expressions in skeletal muscle were not changed.
These findings indicate patterns of RAGE ligands accumulation, RAGE/ligands binding intensities, or inflammation markers changes during aging are organs dependent.
大量证据表明,晚期糖基化终末产物受体(RAGE)相关炎症在衰老过程中起重要作用。然而,大多数研究集中在晚期糖基化终末产物(AGEs)上,而非其他RAGE配体。在本研究中,作者评估了衰老过程中RAGE配体的积累以及RAGE与其配体之间的结合强度在肾脏、肝脏和骨骼肌中是否存在差异。
在12周龄、12月龄和22月龄的C57BL/6 N小鼠中,评估了配体积累、RAGE与其配体之间的结合强度、活化巨噬细胞浸润、M1/M2巨噬细胞表达、乙二醛酶-1表达以及与炎症相关的信号通路。发现RAGE配体的年龄相关积累模式存在器官依赖性。RAGE与其配体在肾脏和肝脏中的结合强度随年龄增加而增加,但在骨骼肌中则保持不变。肾脏和肝脏中活化巨噬细胞的浸润随年龄增加而增加,但在骨骼肌中的浸润没有变化。肾脏和肝脏中M1表达随年龄增加而增加,M2和乙二醛酶-1表达随年龄增加而降低,但它们在骨骼肌中的表达没有变化。
这些发现表明,衰老过程中RAGE配体积累模式、RAGE/配体结合强度或炎症标志物变化存在器官依赖性。