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2018 ; 9
(5
): 533
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Plasma microRNA panel is a novel biomarker for focal segmental glomerulosclerosis
and associated with podocyte apoptosis
#MMPMID29748623
Xiao B
; Wang LN
; Li W
; Gong L
; Yu T
; Zuo QF
; Zhao HW
; Zou QM
Cell Death Dis
2018[May]; 9
(5
): 533
PMID29748623
show ga
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), Bcl-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.