Identification of Age-associated Proteins and Functional Alterations in Human Retinal Pigment Epithelium.
Identification of Age-associated Proteins and Functional Alterations in Human Retinal Pigment Epithelium.
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鉴定与人类视网膜色素上皮的年龄相关蛋白质和功能改变。
DOI：
10.1016/j.gpb.2022.06.001
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发表时间：
2022-08
影响因子：
9.5
通讯作者：
Lei, Bo
中科院分区：
文献类型：
--
作者：
Jin, Xiuxiu;Liu, Jingyang;Wang, Weiping;Li, Jiangfeng;Liu, Guangming;Qiu, Ruiqi;Yang, Mingzhu;Liu, Meng;Yang, Lin;Du, Xiaofeng;Lei, Bo
视网膜色素上皮（Retinal pigment epithelium，RPE）具有营养和支持神经视网膜的重要功能，在年龄相关性视网膜变性的发病机制中起重要作用。然而，在衰老过程中RPE的确切分子变化仍然知之甚少。在这里，我们从分布在广泛年龄范围（10-67岁）的18个眼睛供体中分离出人原代RPE（hRPE）细胞。进行定量蛋白质组学分析以分析其细胞内和分泌蛋白的变化。在ARPE-19和hRPE细胞中揭示了与年龄相关的亚型和年龄相关蛋白，并验证了潜在的年龄相关机制。蛋白质组学数据分析和验证的结果表明，RNF 123和RNF 149相关蛋白的泛素化在保护hRPE细胞免受衰老过程中的氧化损伤中起着重要作用。在较老的hRPE细胞中，细胞凋亡信号相关通路上调，内质网组织下调，在细胞内和分泌的蛋白质组。我们的工作描绘了衰老过程中hRPE细胞的详细分子图像，并为衰老过程中和其他相关临床视网膜条件下RPE的分子特征提供了新的见解。
Retinal pigment epithelium (RPE) has essential functions, such as nourishing and supporting the neural retina, and is of vital importance in the pathogenesis of age-related retinal degeneration. However, the exact molecular changes of RPE during aging remain poorly understood. Here, we isolated human primary RPE (hRPE) cells from 18 eye donors distributed over a wide age range (10–67 years old). A quantitative proteomic analysis was performed to analyze changes in their intracellular and secreted proteins. Age-group related subtypes and age-associated proteins were revealed and potential age-associated mechanisms were validated in ARPE-19 and hRPE cells. The results of proteomic data analysis and verifications suggest that RNF123- and RNF149-related protein ubiquitination plays an important role in protecting hRPE cells from oxidative damage during aging. In older hRPE cells, apoptotic signaling-related pathways were up-regulated, and endoplasmic reticulum organization was down-regulated both in the intracellular and secreted proteomes. Our work paints a detailed molecular picture of hRPE cells during the aging process and provides new insights into the molecular characteristics of RPE during aging and under other related clinical retinal conditions.
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影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
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影响因子：
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