title: Increased expression of lysosome membrane protein 2 in glomeruli of patients with idiopathic membranous nephropathy.
abstract: Urinary microvesicles constitute a rich source of membrane-bound and intracellular proteins that may provide important clues of pathophysiological mechanisms in renal disease. In the current study, we analyzed and compared the proteome of urinary microvesicles from patients with idiopathic membranous nephropathy (iMN), idiopathic focal segmental glomerulosclerosis (iFSGS), and normal controls using an approach that combined both proteomics and pathology analysis. Lysosome membrane protein-2 (LIMP-2) was increased greater than twofold in urinary microvesicles obtained from patients with iMN compared to microvesicles of patients with iFSGS and normal controls. Immunofluorescence analysis of renal biopsies confirmed our proteomics findings that LIMP-2 was upregulated in glomeruli from patients with iMN but not in glomeruli of diseased patients (iFSGS, minimal change nephropathy, IgA nephropathy, membranoproliferative glomerulonephritis) and normal controls. Confocal laser microscopy showed co-localization of LIMP-2 with IgG along the glomerular basement membrane. Serum antibodies against LIMP-2 could not be detected. In conclusion, our data show the value of urinary microvesicles in biomarker discovery and provide evidence for de novo expression of LIMP-2 in glomeruli of patients with iMN.
authors: Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Ilse M
authors: IM
authors: Rood
authors: Kidney Disease Program and Clinical Proteomics Center, University of Louisville, Louisville, KY, USA.
authors: Michael L
authors: ML
authors: Merchant
authors: Kidney Disease Program and Clinical Proteomics Center, University of Louisville, Louisville, KY, USA.
authors: Daniel W
authors: DW
authors: Wilkey
authors: Thermo Fisher Scientific, San Jose, CA, USA.
authors: Terry
authors: T
authors: Zhang
authors: Thermo Fisher Scientific, San Jose, CA, USA.
authors: Vlad
authors: V
authors: Zabrouskov
authors: Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Johan
authors: J
authors: van der Vlag
authors: Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Henry B
authors: HB
authors: Dijkman
authors: Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Brigith K
authors: BK
authors: Willemsen
authors: Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Jack F
authors: JF
authors: Wetzels
authors: Kidney Disease Program and Clinical Proteomics Center, University of Louisville, Louisville, KY, USA.|Veterans Administration Medical Center, Louisville, KY, USA.
authors: Jon B
authors: JB
authors: Klein
authors: Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Jeroen K
authors: JK
authors: Deegens
mesh_terms: D015433:Glomerulonephritis, Membranous / Q000473:pathology / Q000652:urine*; D005923:Glomerulosclerosis, Focal Segmental / Q000473:pathology / Q000652:urine*; D006801:Humans; D007678:Kidney Glomerulus / Q000473:pathology*; D051907:Lysosomal Membrane Proteins / Q000032:analysis* / Q000652:urine*; D051116:Receptors, Scavenger / Q000032:analysis*
chemical_list: D051907:Lysosomal Membrane Proteins; D051116:Receptors, Scavenger; C074299:SCARB2 protein, human
keywords: Biomedicine; Extracellular vesicles; Focal segmental glomerulosclerosis; Idiopathic membranous nephropathy; LIMP-2; Microvesicles