Circulating and urinary microRNA profile in focal segmental glomerulosclerosis: a pilot study

Abstract

Background MicroRNAs (miRNAs) are non-coding RNA molecules that play important roles in the pathogenesis of various kidney diseases. We investigated whether patients with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) have distinct circulating and urinary miRNA expression profiles that could lead to potential development of noninvasive biomarkers of the disease. Materials and methods Exosome miRNAs were extracted from plasma and urine samples of patients with primary FSGS (n=16) or MCD (n=5) and healthy controls (n=5). Differences in miRNA abundance were examined using Affymetrix GeneChip miRNA 3.0 arrays. QRT-PCR was used to validate the findings from the array. Results Comparison analysis of FSGS versus MCD revealed 126 and 155 differentially expressed miRNAs in plasma and in urine, respectively. Only 38 of these miRNAs were previously cited, whereas the remaining miRNAs have not been described. Comparison analysis showed that a significant number of miRNAs were down-regulated in both plasma and urine samples of FSGS patients compared to those with MCD. Plasma levels of miR-30b, miR-30c, miR-34b, miR-34c, and miR-342, and urine levels of mir-1225-5p were up-regulated in MCD patients compared to FSGS patients and controls (p<0.001). Urinary levels of mir-1915 and miR-663 were down-regulated in FSGS patients compared to MCD and controls (p<0.001), whereas the urinary levels of miR-155 were up-regulated in FSGS patients when compared to MCD patients and controls (p<0.005). Conclusions Patients with FSGS and MCD have a unique circulating and urinary miRNA profile. The diagnostic and prognostic potential of miRNAs in FSGS and MCD warrants further studies.

Urinary exosome-derived microRNAs reflecting the changes of renal function and histopathology in dogs

“…reported that miR-29c levels in UExos correlated with the chronicity and glomerular sclerosis in human patients with lupus nephritis11. Furthermore, miR-1915 and miR-663 levels in UExo were downregulated in patients with focal segmental glomerulosclerosis compared to healthy controls, whereas those of miR-155 were upregulated in these patients12. We also reported altered levels of miR-26a and miR-146a in the urine of CKD model mice23.…”

Clinical verification of a novel urinary microRNA panal: 133b, -342 and -30 as biomarkers for diabetic nephropathy identified by bioinformatics analysis

“…miR-342-3p had been found to be upregulated in prion disease [27], cancer colon [28], irritable bowel disease [29] obesity [30], T1DM and T2DM [24]. In like manar, plasma levels of miR-30b, miR-30c and miR-342 were up regulated in patients with minimal change disease compared to patients with focal Segmental Glomerulosclerosis(FGSC) and controls [31]. In another study, the expression of miR-342-3p was significantly decreased in systemic lupus erythromatous patients with active nephritis and all of the signature miRNA À342 target genes are in the transforming growth factor b signaling pathways [32,33].…”

Identification, Confirmation, and Replication of Novel Urinary MicroRNA Biomarkers in Lupus Nephritis and Diabetic Nephropathy

“…The association between miR-2861, miR-1915-3p, and miR-4532 followed a near dose–response relationship with IFTA highlighted by the lower urinary levels per increasing grade of IFTA, and may suggest a role for fibrosis formation in DN. Previous studies reported the up-regulation of miR-2861 and miR-1915-3p in patients with type 2 diabetes with microalbuminuria (31) and down-regulation of miR-1915-3p in focal segmental glomerulosclerosis patients (34). However, these miRNAs were assessed in urinary exosomes; very few patients were enrolled in these studies (n < 20), and none of them had biopsy-proven DN.…”