Molecular profiling in IgA nephropathy and focal and segmental glomerulosclerosis

• Published in: Physiological research Vol. 67; no. 1; pp. 93 - 105
• Main Authors: Tycová, I, Hrubá, P, Maixnerová, D, Girmanová, E, Mrázová, P, Straňavová, L, Zachoval, R, Merta, M, Slatinská, J, Kollár, M, Honsová, E, Tesař, V, Viklický, O
• Format: Journal Article
• Language: English
• Published: Czech Republic Institute of Physiology 01-01-2018
• Subjects: Adult; Aged; Apoptosis; Bax protein; Biomarkers; Biopsy; CCL19 protein; Chemokines; Cohort Studies; Disease; Endothelin 1; Endothelins; Epidermal growth factor; FasL protein; Female; Follow-Up Studies; Gene expression; Gene Expression Profiling - methods; Glomerulonephritis, IGA - genetics; Glomerulonephritis, IGA - pathology; Glomerulosclerosis, Focal Segmental - genetics; Glomerulosclerosis, Focal Segmental - pathology; Heme; Humans; IgA nephropathy; Immunoglobulin A; Immunoglobulins; Interleukin 1; Interleukin 18; Kidney - metabolism; Kidney - pathology; Kidney cancer; Laboratories; Ligands; Male; Middle Aged; Nephrology; Oxygenase; Pathogenesis; Patients; Prospective Studies; Protein-tyrosine-phosphatase; Proteins; Rodents; Transplants & implants; Vascular endothelial growth factor
• ISSN: 0862-8408; 1802-9973
• DOI: 10.33549/physiolres.933670

The aim of the study was to characterize by molecular profiling two glomerular diseases: IgA nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS) and to identify potential molecular markers of IgAN and FSGS progression. The expressions of 90 immune-related genes were compared in biopsies of patients with IgAN (n=33), FSGS (n=17) and in controls (n=11) using RT-qPCR. To identify markers of disease progression, gene expression was compared between progressors and non-progressors in 1 year follow-up. The results were verified on validation cohort of patients with IgAN (n=8) and in controls (n=6) using laser-capture microdissection, that enables to analyze gene expression separately for glomeruli and interstitium. In comparison to controls, patients with both IgAN and FSGS, had lower expression of BAX (apoptotic molecule BCL2-associated protein) and HMOX-1 (heme oxygenase 1) and higher expression of SELP (selectin P). Furthermore, in IgAN higher expression of PTPRC (protein-tyrosine phosphatase, receptor-type C) and in FSGS higher expression of BCL2L1 (regulator of apoptosis BCL2-like 1) and IL18 compared to control was observed. Validation of differentially expressed genes between IgAN and controls on another cohort using laser-capture microdissection confirmed higher expression of PTPRC in glomeruli of patients with IgAN. The risk of progression in IgAN was associated with higher expression EDN1 (endothelin 1) (AUC=0.77) and FASLG (Fas ligand) (AUC=0.82) and lower expression of VEGF (vascular endothelial growth factor) (AUC=0.8) and in FSGS with lower expression of CCL19 (chemokine (C-C motif) ligand 19) (AUC=0.86). Higher expression of EDN1 and FASLG along with lower expression of VEGF in IgAN and lower expression of CCL19 in FSGS at the time of biopsy can help to identify patients at risk of future disease progression.