Proteomic Analysis of Plasma sEVs Reveals That TNFAIP8 Is a New Biomarker of Cell Proliferation in Diabetic Retinopathy

被引：20
作者：
Xiao, Jing [1 ,2 ]
Zhang, Hui [1 ,2 ]
Yang, Fuhua [1 ,2 ]
Xiao, Mengran [1 ,2 ]
Zhou, Lei [3 ,4 ,5 ]
Yu, Rongguo [1 ,2 ]
Shao, Xianfeng [1 ,2 ]
Ea, Vicki [1 ,2 ]
Su, Lin [1 ,2 ]
Zhang, Xiaomin [1 ,2 ]
Li, Xiaorong [1 ,2 ]
机构：
[1] Tianjin Med Univ Eye Hosp, Tianjin Int Joint Res & Dev Ctr Ophthalmol & Vis, Eye Inst, Tianjin Key Lab Retinal Funct & Dis, Tianjin 300384, Peoples R China
[2] Tianjin Med Univ Eye Hosp, Sch Optometry, Tianjin 300384, Peoples R China
[3] Singapore Eye Res Inst, Singapore, Singapore
[4] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore
[5] Natl Univ Singapore, Ophthalmol & Visual Sci Acad Clin Res Program, Duke NUS Med Sch, Singapore 119077, Singapore
来源：
JOURNAL OF PROTEOME RESEARCH | 2021年 / 20卷 / 03期
基金：
中国国家自然科学基金;
关键词：
proteomic; diabetic retinopathy; plasma sEVs; TNFAIP8; proliferation; biomarker; MEDIATED APOPTOSIS; AQUEOUS-HUMOR; EXOSOMES; EXPRESSION; AUTOFLUORESCENCE; SEVERITY; IMMUNITY; SCC-S2; FAMILY; MMP-1;
D O I：
10.1021/acs.jproteome.0c01048
中图分类号：
Q5 [生物化学];
学科分类号：
071010 ; 081704 ;
摘要：
Small extracellular vesicles (sEVs) derived from the plasma have been increasingly recognized as important vehicles of intercellular communication and potential sources of new biomarkers for multiple diseases. In this study, proteomic profiles of plasma sEVs from normal subjects and diabetic patients with or without diabetic retinopathy (DR) were systematically compared using iTRAQ-based quantitative proteomics. Among a total of 901 identified proteins in plasma sEVs (false discovery rate (FDR) < 1%), 90 proteins were found to have significantly changed levels in DR. Based on the findings from the proteomic analysis, the role of tumor necrosis factor-alpha-induced protein 8 (TNFAIP8) in promoting human retinal microvascular endothelial cell (HRMEC) proliferation was investigated. The enzyme-linked immunosorbent assay (ELISA) showed that TNFAIP8 levels in plasma sEVs and vitreous are elevated in DR, whereas not statistically different in large EVs (lEVs) and plasma. In addition, in vitro experiments demonstrated that 4-hydroxynonenal (4-HNE) increased the expression of TNFAIP8 in HRMECs. TNFAIP8 significantly increased HRMECs cell viability and promote cell migration and tube formation, and the depletion of TNFAIP8 impaired HRMEC proliferation. We demonstrated that TNFAIP8 in plasma sEVs could be used as a potential biomarker of DR. Functional studies suggested that TNFAIP8 might be an important mediator of angiogenesis in DR.
引用
收藏
页码：1770 / 1782
页数：13
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