title: Proteomic profiling of human plasma exosomes identifies PPARgamma as an exosome-associated protein.
abstract: Exosomes are nanovesicles that are released from cells as a mechanism of cell-free intercellular communication. Only a limited number of proteins have been identified from the plasma exosome proteome. Here, we developed a multi-step fractionation scheme incorporating gel exclusion chromatography, rate zonal centrifugation through continuous sucrose gradients, and high-speed centrifugation to purify exosomes from human plasma. Exosome-associated proteins were separated by SDS-PAGE and 66 proteins were identified by LC-MS/MS, which included both cellular and extracellular proteins. Furthermore, we identified and characterized peroxisome proliferator-activated receptor-gamma (PPARgamma), a nuclear receptor that regulates adipocyte differentiation and proliferation, as well as immune and inflammatory cell functions, as a novel component of plasma-derived exosomes. Given the important role of exosomes as intercellular messengers, the discovery of PPARgamma as a component of human plasma exosomes identifies a potential new pathway for the paracrine transfer of nuclear receptors.
authors.affiliation: Pulmonary and Vascular Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Building, Room 6D03, MSC 1590, Bethesda, MD 20892, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Looze
authors.forename: David
authors.initials: D
authors.lastname: Yui
authors.forename: Lester
authors.initials: L
authors.lastname: Leung
authors.forename: Matthew
authors.initials: M
authors.lastname: Ingham
authors.forename: Maryann
authors.initials: M
authors.lastname: Kaler
authors.forename: Xianglan
authors.initials: X
authors.lastname: Yao
authors.forename: Wells W
authors.initials: WW
authors.lastname: Wu
authors.forename: Rong-Fong
authors.initials: RF
authors.lastname: Shen
authors.forename: Mathew P
authors.initials: MP
authors.lastname: Daniels
authors.forename: Stewart J
authors.initials: SJ
authors.lastname: Levine
mesh_terms: D002853:Chromatography, Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D055354:Exosomes / Q000378:metabolism*; D006801:Humans; D053419:Lipoproteins, IDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D013058:Mass Spectrometry; D047495:PPAR gamma / Q000097:blood*; D040081:Protein Array Analysis; D040901:Proteomics; D044967:Serum / Q000378:metabolism*
chemical_list: D053419:Lipoproteins, IDL; D008079:Lipoproteins, VLDL; D047495:PPAR gamma