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

Jing Xiao, Hui Zhang, Fuhua Yang, Mengran Xiao, Lei Zhou, Rongguo Yu, Xianfeng Shao, Vicki Ea, Lin Su, Xiaomin Zhang, Xiaorong Li

Research output: Journal article publicationJournal articleAcademic researchpeer-review

4 Citations (Scopus)


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-α-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.

Original languageEnglish
Pages (from-to)1770-1782
Number of pages13
JournalJournal of Proteome Research
Issue number3
Publication statusPublished - 5 Mar 2021
Externally publishedYes


  • biomarker
  • diabetic retinopathy
  • plasma sEVs
  • proliferation
  • proteomic

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry


Dive into the research topics of 'Proteomic Analysis of Plasma sEVs Reveals That TNFAIP8 Is a New Biomarker of Cell Proliferation in Diabetic Retinopathy'. Together they form a unique fingerprint.

Cite this