Urinary Extracellular Vesicles: Potential Biomarkers of Renal Function in Diabetic Patients

Figure 4

Proteomic analysis of urinary extracellular vesicles: mass spectrometry results from representative samples. (a) Venn diagram shows that in EVs from controlled diabetic patient with microalbuminuria there is a large number of unique proteins (), in a healthy control and in an uncontrolled diabetic patient with macroalbuminuria the number of unique proteins is very low () [20]. (b) Protein-to-protein interaction analysis of common 45 proteins selected from Venn diagram shows the central role of albumin among urinary EV-related proteins; the list of submitted proteins is available in a supplementary data file (Supplementary Table ) [22]. (c, d) Gene Ontology analysis showed that most of identified proteins are related to extracellular region or they are related to membrane organelles (exosomes); their localization corresponds with molecular function (receptors and transport proteins) [19]. A1BG: alpha-1-B glycoprotein; A2M: alpha-2-macroglobulin; ACTB: actin, beta; AFM: afamin; ALB: albumin; AMBP: alpha-1-microglobulin/bikunin precursor; ANPEP: alanyl (membrane) aminopeptidase; APOD: apolipoprotein D; AZGP1: alpha-2-glycoprotein 1, zinc-binding; CD59: CD59 molecule, complement; regulatory protein; CP: ceruloplasmin; GC: group-specific component (vitamin D binding protein); HBA1: hemoglobin, alpha 1; HBB: hemoglobin, beta; HP: haptoglobin; HPX: hemopexin; HSPG2: heparan sulfate proteoglycan 2; IGJ: immunoglobulin J polypeptide; IGLL5: immunoglobulin lambda-like polypeptide 5; KRT1: keratin 1; KRT2: keratin 2; KRT9: keratin 9; KRT10: keratin 10; LRG1: leucine-rich alpha-2-glycoprotein 1; MASP2: mannan-binding lectin serine peptidase 2; MUC1: mucin 1; ORM1: orosomucoid 1; ORM2: orosomucoid 2; PLG: plasminogen; PODXL: podocalyxin-like; POTEE: POTE ankyrin domain family member E; SERPINA1: serpin peptidase inhibitor, clade A, member 1; SERPINA3: serpin peptidase; inhibitor, clade A, member 3; TF: transferrin; UMOD: uromodulin.

(a)

(b)

(c)

(d)