HMGB1 and Caveolin-1 related to RPE cell senescence in age-related macular degeneration
HMGB1 and Caveolin-1 related to RPE cell senescence in age-related macular degeneration
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HMGB1和Caveolin-1与年龄相关性黄斑变性中RPE细胞衰老相关
DOI：
10.18632/aging.102039
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发表时间：
2019-07
期刊：
影响因子：
--
通讯作者：
Xiaorong Li
中科院分区：
文献类型：
--
作者：
Shuo Sun;Bincui Cai;Yao Li;Wenqi Su;Xuzheng Zhao;Boteng Gong;Zhiqing Li;Xiaomin Zhang;Yalin Wu;Chao Chen;Stephen H. Tsang;Jin Yang;Xiaorong Li
脂褐素在视网膜色素上皮(RPE)中的积聚被认为是老年性黄斑变性(AMD)中RPE功能障碍和衰老的主要原因，而N-视黄亚甲基-N-视黄醇乙醇胺(A2E)是老年人眼脂褐素中发现的主要荧光团。在这里，人类诱导的多能干细胞(IPSC)-RPE是从健康个体中产生的，以揭示与A2E相关的RPE细胞衰老相关的蛋白质组变化。通过对A2E处理的IPSC-RPE进行蛋白质组学分析，鉴定了一种新的RPE细胞衰老相关蛋白--高迁移率族蛋白1(HMGB1)。此外，HMGB1上调Caveolin-1，这也与RPE细胞的衰老有关。为探讨A2E作用下RPE细胞HMGB1和Caveolin-1表达的变化是否有助于RPE细胞的衰老，用A2E刺激人ARPE-19细胞，观察HMGB1、Caveolin-1、紧密连接蛋白的表达和衰老表型。抑制HMGB1可减轻A2E诱导的细胞衰老。观察RPE细胞的迁移情况。值得注意的是，当A2E小于或等于10μM时，HMGB1和Caveolin-1蛋白表达上调，HMGB1易位；当A2E大于10μM时，Caveolin-1表达下调。提示A2E诱导的HMGB1、、小窝蛋白-1和HMGB1释放上调可能与视网膜色素上皮细胞衰老有关，在老年性黄斑变性的发病机制中起一定作用。
Accumulation of lipofuscin in the retinal pigment epithelium (RPE) is considered a major cause of RPE dysfunction and senescence in age-related macular degeneration (AMD), and N-retinylidene-N-retinylethanolamine (A2E) is the main fluorophore identified in lipofuscin from aged human eyes. Here, human-induced pluripotent stem cell (iPSC)-RPE was generated from healthy individuals to reveal proteomic changes associated with A2E-related RPE cell senescence. A novel RPE cell senescence-related protein, high-mobility group box 1 (HMGB1), was identified based on proteomic mass spectrometry measurements on iPSC-RPE with A2E treatment. Furthermore, HMGB1 upregulated Caveolin-1, which also was related RPE cell senescence. To investigate whether changes in HMGB1 and Caveolin-1 expression under A2E exposure contribute to RPE cell senescence, human ARPE-19 cells were stimulated with A2E; expression of HMGB1, Caveolin-1, tight junction proteins and senescent phenotypes were verified. HMGB1 inhibition alleviated A2E induced cell senescence. Migration of RPE cells was evaluated. Notably, A2E less than or equal to 10μM induced both HMGB1 and Caveolin-1 protein upregulation and HMGB1 translocation, while Caveolin-1 expression was downregulated when there was more than 10μM A2E. Our data indicate that A2E-induced upregulation of HMGB1、Caveolin-1 and HMGB1 release may relate to RPE cell senescence and play a role in the pathogenesis of AMD.
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影响因子：
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