Plasma microRNA panel is a novel biomarker for focal segmental glomerulosclerosis and associated with podocyte apoptosis

Focal segmental glomerulosclerosis (FSGS) is a frequent glomerular disease, and is the common cause of nephrotic syndrome. However, there is no validated diagnostic blood biomarker for FSGS Here, we performed a real time PCR based high throughput miRNA profiling to identify the plasma signature for FSGS We found four miRNAs (miR-17, miR-451, miR-106a, and miR-19b) were significantly downregulated in the plasma of FSGS patients (n = 97) compared with healthy controls (n = 124) in the training, validation, and blinded test phases The miRNA panel produced an AUC value of 0.82, and was associated with FSGS severity and histologic classification A three-miRNA panel, including miR -17, miR-451, and miR-106a was related to FSGS remission Furthermore, the downregulation of plasma-miRNA signature was not detected in disease controls (n = 119) such as IgA nephropathy (IgAN), mesangial proliferative glomerulonephritis (MSPGN), and membranous nephropathy (MN), and the miRNA panel discriminated between FSGS and disease controls Pathway analysis showed that the four-miRNA panel may cooperatively regulate the pathways involved in the development of FSGS, such as apoptosis We identified that phosphatase and tensin homolog (PTEN), Bel-2-like protein 11 (BCL2L11), and chemokine (C-X-C motif) ligand 14 (CXCL14) were targets of miR-106a in human podocyte Additionally, miR-106a overexpression suppressed podocyte apoptosis in vitro and the downregulation of four-miRNA panel probably resulted in the enhanced apoptosis in podocyte during FSGS development Taken together, our data show that the plasma-miRNA panel is a potential independent diagnostic and prognostic factor for FSGS Above miRNAs are involved in FSGS pathogenesis through regulating podocyte apoptosis.