The Novel Diagnostic Biomarkers for Focal Segmental Glomerulosclerosis

Abstract

Background. Focal segmental glomerulosclerosis (FSGS) is a glomerular injury with various pathogenic mechanisms. Urine proteome panel might help in noninvasive diagnosis and better understanding of pathogenesis of FSGS. Method. We have analyzed the urine sample of 11 biopsy-proven FSGS subjects, 8 healthy controls, and 6 patients with biopsy-proven IgA nephropathy (disease controls) by means of liquid chromatography tandem mass spectrometry (nLC-MS/MS). Multivariate analysis of quantified proteins was performed by principal component analysis (PCA) and partial least squares (PLS). Results. Of the total number of 389 proteins, after multivariate analysis and additional filter criterion and comparing FSGS versus IgA nephropathy and healthy subjects, 77 proteins were considered as putative biomarkers of FSGS. CD59, CD44, IBP7, Robo4, and DPEP1 were the most significant differentially expressed proteins. These proteins are involved in pathogenic pathways: complement pathway, sclerosis, cell proliferation, actin cytoskeleton remodeling, and activity of TRPC6.There was complete absence of DPEP1 in urine proteome of FSGS subjects compared with healthy and disease controls. DPEP1 acts via leukotrienes on TRPC6 and results in increased podocyte motility and proteinuria. Conclusion. The results suggest a panel of candidate biomarkers for noninvasive diagnosis of FSGS, while complete absence of DPEP1 might represent a novel marker of FSGS.

Clinicopathological correlations of mesenteric fibrosis and evaluation of a novel biomarker for fibrosis detection in small bowel neuroendocrine neoplasms

“…Moreover, CD59 is a regulator of complement activation and inhibits the formation of the membrane attack complex. The complement system is involved not only in innate immunity and adaptive responses but also in tissue repair and fibrosis [21,22]. Thus, CD59 may be viewed as a regulator of fibrosis.…”

The Robo4 cytoplasmic domain is dispensable for vascular permeability and neovascularization

“…Robo4 encodes a 140 kDa protein that comprises a 60 kDa extracellular domain (ECD) with two immunoglobulin (Ig)-like domains and two fibronectin-repeat regions, a transmembrane domain and an intracellular domain (ICD) devoid of known catalytic sequences2. Robo4 is upregulated in endothelium of embryonic blood vessels and in micro-vessels of patients with tumours and vascular injury, but is also seen in quiescent endothelium1234567. Its endothelial-specific expression is regulated by activator protein-1 (AP-1) binding to a 3 kb fragment of the promoter789.…”

Proteomics and glomerulonephritis: A complementary approach in renal pathology for the identification of chronic kidney disease related markers

“…Finally, Nafar et al. compared urine samples from 11 patients with FSGS, six patients with IgAN, and eight HCs using nano‐LC‐MS/MS . Among the 77 proteins considered as putative biomarkers of FSGS, CD59, CD44, IBP7, Robo4, and DPEP1 were the most significantly differentially expressed proteins.…”

“…Among the 54 significant proteins identified, ribonuclease 2 and haptoglobin had the greatest fold change in terms of overrepresentation and underrepresentation in patients with the best and worse prognoses, respectively. Finally, Nafar et al compared urine samples from 11 patients with FSGS, six patients with IgAN, and eight HCs using nano-LC-MS/MS [66]. Among the 77 proteins considered as putative biomarkers of FSGS, CD59, CD44, IBP7, Robo4, and DPEP1 were the most significantly differentially expressed proteins.…”