The proteome profiling of EVs originating from senescent cell model using quantitative proteomics and parallel reaction monitoring

Fengjuan Liu; Shengliang Ye; Peng Jiang; Wei Zhang; Zongkui Wang; Changqing Li

doi:10.1016/j.jprot.2022.104669

The proteome profiling of EVs originating from senescent cell model using quantitative proteomics and parallel reaction monitoring

J Proteomics. 2022 Aug 30:266:104669. doi: 10.1016/j.jprot.2022.104669. Epub 2022 Jul 2.

Authors

Fengjuan Liu¹, Shengliang Ye², Peng Jiang³, Wei Zhang⁴, Zongkui Wang⁵, Changqing Li⁶

Affiliations

¹ Institute of blood transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu 610052, China. Electronic address: fengjuan.liu@ibt.pumc.edu.cn.
² Institute of blood transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu 610052, China. Electronic address: shengliang.ye@ibt.pumc.edu.cn.
³ Institute of blood transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu 610052, China. Electronic address: peng.jiang@ibt.pumc.edu.cn.
⁴ Institute of blood transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu 610052, China.
⁵ Institute of blood transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu 610052, China. Electronic address: zongkui.wang@ibt.pumc.edu.cn.
⁶ Institute of blood transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu 610052, China. Electronic address: lcq@ibt.pumc.edu.cn.

PMID: 35788408
DOI: 10.1016/j.jprot.2022.104669

Abstract

Senescence is the inevitable biological processes and is also considered as the biggest risk factor for the development of age - related diseases (ARDs) and geriatric syndrome (GS). Senescence is also known as inflammaging because it is characterized by persistent, long-term, low-grade inflammation named senescence-associated secretory phenotype (SASP). However, the mechanism for the persistence of inflammaging remains largely unclear. To explore the role of extracellular vesicles (EVs) in senescence/inflammaging, we established the cellular senescence model and performed TMT-based comparative quantitative proteomics and parallel reaction monitoring (PRM) to reveal the changes of EVs between young cells and senescent cells. A total of 3966 proteins were quantifiable, of which 132 were up-regulated, 144 were down-regulated, compared with the young cells. Subsequently, we chose 19 proteins involved in inflammation or proliferation to carry out PRM validation analysis. The result indicated that proteins promoting NF-κB signal pathway were up-regulated, and proteins promoting cell proliferation were down-regulated. The study provided a comprehensive altered proteomics profiles of EVs from senescent cells, and the result showed that EVs could serve as information carrier for further research on the pathogenesis and progression of senescence/inflammaging. SIGNIFICANCE: The mechanism of inflammaging occurrence and development has yet been clear. Therefore, this study attempts to provide an improved understanding of inflammaging from the perspective of EVs. The proteomics analysis revealed that the most changed proteins were connected to inflammation signaling pathways, cell growth and cell death, and PRM analysis results showed that proteins involved in NF-κB signal pathway and cell proliferation were more changed. The research systematically analyzed the profiles of proteins in senescence cell model, and the result indicated that further research should focus on the relationship between EVs and senescence/inflammaging.

Keywords: Extracellular vesicles; Inflammaging; Parallel reaction monitoring; SASP; Senescence; TMT labelling.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cellular Senescence / physiology
Extracellular Vesicles* / metabolism
Humans
Inflammation / metabolism
NF-kappa B* / metabolism
Proteome / metabolism
Proteomics

Substances

NF-kappa B
Proteome