晚期糖基化终末产物通过AGE/RAGE/ILK途径加速肾移植后的动脉硬化。
Advanced glycation end products accelerate arteriosclerosis after renal transplantation through the AGE/RAGE/ILK pathway.
作者信息
Liu Xuzhong, Liu Kun, Wang Zijie, Liu Chao, Han Zhijian, Tao Jun, Lu Pei, Wang Jun, Wu Bian, Huang Zhengkai, Yin Changjun, Gu Min, Tan Ruoyun
机构信息
Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province 210029, China.
Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province 210029, China; Department of Urology, Huai'an First People's Hospital, 6 Beijing West Road, Huai'an, Jiangsu Province 223300, China.
出版信息
Exp Mol Pathol. 2015 Oct;99(2):312-9. doi: 10.1016/j.yexmp.2015.07.009. Epub 2015 Jul 23.
BACKGROUND
The effects of advanced glycation end products (AGEs) on arteriosclerosis (AS) after kidney transplantation and the molecular mechanisms involved remain unclear.
METHODS
Samples were collected from 30 healthy volunteers and 30 renal transplant recipients (RTRs) to determine the levels of AGEs and to observe both histological changes and α-smooth muscle actin (α-SMA) and osteopontin (OPN) expression. Furthermore, we analyzed α-SMA, OPN and integrin-linked kinase (ILK) in rat vascular smooth muscle cells (VSMCs) that were treated with AGEs and in ILK plasmid transfected rat VSMCs treated with AGEs. Finally, we measured the expression of ILK and the receptor for advanced glycation end (RAGE) products in rat VSMCs treated with AGEs and an anti-RAGE antibody.
RESULTS
Significant differences in the histological changes, serum AGEs, and expression of α-SMA and OPN in arterial walls were noted between healthy volunteers and RTRs. Significant OPN and ILK overexpression and reduced α-SMA expression were detected in a time-dependent manner in rat VSMCs after treatment with AGEs. Similar outcomes were observed regarding the overexpression of ILK, and these results could be prevented via RAGE inhibition.
CONCLUSIONS
AGEs may play a critical role in the formation and progression of AS after renal transplantation by inducing VSMCs-to-osteoblast trans-differentiation through the AGE/RAGE/ILK pathway.
背景
晚期糖基化终末产物（AGEs）对肾移植后动脉硬化（AS）的影响及其相关分子机制尚不清楚。
方法
收集30名健康志愿者和30名肾移植受者（RTRs）的样本，以测定AGEs水平，并观察组织学变化以及α平滑肌肌动蛋白（α-SMA）和骨桥蛋白（OPN）的表达。此外，我们分析了用AGEs处理的大鼠血管平滑肌细胞（VSMCs）以及用AGEs处理的ILK质粒转染大鼠VSMCs中的α-SMA、OPN和整合素连接激酶（ILK）。最后，我们测量了用AGEs和抗RAGE抗体处理的大鼠VSMCs中ILK和晚期糖基化终末产物受体（RAGE）的表达。
结果
健康志愿者和RTRs在组织学变化、血清AGEs以及动脉壁中α-SMA和OPN的表达方面存在显著差异。用AGEs处理后的大鼠VSMCs中，OPN和ILK显著过表达，α-SMA表达呈时间依赖性降低。在ILK过表达方面也观察到类似结果，并且这些结果可通过RAGE抑制来预防。
结论
AGEs可能通过AGE/RAGE/ILK途径诱导血管平滑肌细胞向成骨细胞转分化，在肾移植后AS的形成和进展中起关键作用。
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