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Journal article
Proteome characterization of small extracellular vesicles from spared nerve injury model of neuropathic pain
Journal of proteomics, v 211, 103540
16 Jan 2020
PMID: 31669360
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Exosomes are 30–150 nm extracellular vesicles mediating intercellular communication. Disease states can alter exosome composition affecting the message carried and thereby, its functional impact. The objective of this study was to identify proteins present in these vesicles in a mouse model of neuropathic pain induced by spared nerve injury (SNI). Small extracellular vesicles (sEVs) were purified from serum four weeks after SNI surgery and the protein composition was determined using tandem mass spectrometry and cytokine array. Proteomic analysis detected 274 gene products within sEVs. Of these, 24 were unique to SNI model, 100 to sham surgery control and five to naïve control samples. In addition to commonly expressed sEVs proteins, multiple members of serpin and complement family were detected in sEVs. Cytokine profiling using a membrane-based antibody array showed significant upregulation of complement component 5a (C5a) and Intercellular Adhesion Molecule 1 (ICAM-1) in sEVs from SNI model compared to sham control. We observed a differential distribution of C5a and ICAM-1 within sEVs and serum between sham and SNI, indicating changes from local or paracrine to long distance signaling under neuropathic pain. Our studies suggest critical roles for cargo sorting of vesicular proteins in mediating signaling mechanisms underlying neuropathic pain.
Approximately 100 million U.S. adults are burdened by chronic pain. Neuropathic pain resulting from injury or dysfunction of the nervous system is challenging to treat. Unlike acute pain that resolves over time, chronic pain persists resulting in changes in the peripheral and central nervous system. The transport of biomolecular cargo comprised of proteins and RNAs by small extracellular vesicles (sEVs) including exosomes has been proposed to be a fundamental mode of intercellular communication. To obtain insights on the role of exosome-mediated information transfer in the context of neuropathic pain, we investigated alterations in protein composition of sEVs in a mouse model of neuropathic pain induced by spared nerve injury (SNI). Our studies using mass spectrometry and cytokine array show that sEVs from SNI model harbor unique proteins. We observed an upregulation of C5a and ICAM-1 in exosomes from SNI model compared to control. There was a differential distribution of C5a and ICAM-1 within exosomes and serum, between control and SNI suggesting a switch from local to long distance signaling. Our studies suggest critical roles for cargo sorting of vesicular proteins in mediating signaling under neuropathic pain.
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•Proteomic analysis of small extracellular vesicles or exosomes in mouse spared nerve injury model of neuropathic pain.•Of the 274 gene products detected, 24 were unique to exosomes from SNI model.•Cytokine profiling showed upregulation of C5a and ICAM-1 in exosomes from SNI model compared to sham control.•Distribution of C5a and ICAM-1 within exosomes and serum differed between sham and SNI.•Alterations in cargo sorting of vesicular proteins observed under neuropathic pain.
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Details
- Title
- Proteome characterization of small extracellular vesicles from spared nerve injury model of neuropathic pain
- Creators
- Renee Jean-Toussaint - Department of Pharmacology & Physiology, Drexel University College of Medicine, Philadelphia, PA, USAYuzhen Tian - Department of Pharmacology & Physiology, Drexel University College of Medicine, Philadelphia, PA, USAAmrita Datta Chaudhuri - Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USANorman J Haughey - Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USAAhmet Sacan - School of Biomedical Engineering, Science & Health Systems, Drexel University, Philadelphia, PA, USASeena K Ajit - Department of Pharmacology & Physiology, Drexel University College of Medicine, Philadelphia, PA, USA
- Publication Details
- Journal of proteomics, v 211, 103540
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology; School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000500375300009
- Scopus ID
- 2-s2.0-85074240267
- Other Identifier
- 991014878310204721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemical Research Methods