Title:Identification and Characterization of New Proteins in Podocyte Dysfunction of Membranous Nephropathy by Proteomic Analysis of Renal Biopsy
VOLUME: 11 ISSUE: 1
Author(s):Ligabue Giulia, Magistroni Riccardo, Cantu’ Marco, Genovese Filippo, Lupo Valentina, Cavazzini Fabrizio, Furci Luciana and Cappelli Gianni
Affiliation:Riccardo Magistroni, Division of Nephrology Dialysis and Renal Transplantation, via del Pozzo 71, 41124 Modena (MO), Italy.
Keywords:Interstitial fluid, membranous nephropathy, nephrotic syndrome, podocyte, proteinuria, proteomics.
Abstract:Interstitial fluid, obtained by gentle centrifugation of the renal biopsy specimen, is highly enriched in elements
directly secreted by the kidney tissue and is suitable for proteomic analysis. Here we describe the first clinical application
of renal interstitial fluid analysis in a subset of samples obtained from patients affected by idiopathic membranous
nephropathy.
We included in the study fifty-one patients with different pathologic diagnoses. We identified the proteomic pattern of
idiopathic membranous nephropathy with mass spectrometry analysis by comparing these samples with two controls:
normal kidney and IgA nephropathy. Proteomic results were validated by immunofluorescence analysis of renal tissues
and Western blot of serum, urines and podocyte cell cultures.
We observed an increased expression of PDZ and LIM domain protein 5 (PDLI5) and LIM domain binding protein 3
(LDB3) providing first evidence of the differential expression of these LIM domain-related proteins in kidney and urines
of patients with idiopathic membranous nephropathy.
Interstitial fluid can be considered a valuable biological fluid in the discovery phase of biomarkers. In order to validate its
clinical use, it is pivotal to assess the availability of the biomarkers in ‘usual’ samples: blood and/or urine. PDLI5 and
LDB3 share a common LIM domain suggesting a possible role in the cytoskeleton organization and they appear upregulated
in glomeruli of patients affected by idiopathic membranous nephropathy. Furthermore the two proteins become
highly abundant in the urine of patients affected by idiopathic membranous nephropathy. In conclusion, our approach may
be considered a novel method for identifying candidate biomarkers for patients suffering from membranous nephropathy
and other glomerulonephrites.
