An Exosomal Urinary miRNA Signature for Early Diagnosis of Renal Fibrosis in Lupus Nephritis

• Published in: Cells (Basel, Switzerland) Vol. 8; no. 8; p. 773
• Main Authors: Solé, Cristina, Moliné, Teresa, Vidal, Marta, Ordi-Ros, Josep, Cortés-Hernández, Josefina
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25.07.2019; MDPI
• Subjects: Adult; Binding sites; Biomarkers; Biopsy; Collagen (type I); Early Diagnosis; End-stage renal disease; Exosomes; Exosomes - metabolism; Female; Fibrosis; Gene Expression Profiling; Genes; Histology; Humans; Immunohistochemistry; Kidney diseases; Liquid Biopsy; Lupus; Lupus nephritis; Lupus Nephritis - diagnosis; Lupus Nephritis - etiology; Male; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; MicroRNAs - urine; Microscopy; miRNA; multi-marker panel; Nephritis; Phenotyping; Real-Time Polymerase Chain Reaction; renal fibrosis; Smad3 protein; Sp1 protein; urinary exosomes; Urine; Young Adult; United States > US; lupus nephritis; urinary exosomes; renal fibrosis; multi-marker panel
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells8080773

For lupus nephritis (LN) management, it is very important to detect fibrosis at an early stage. Urinary exosomal miRNAs profiling can be used as a potential multi-marker phenotyping tool to identify early fibrosis. We isolated and characterised urinary exosomes and cellular pellets from patients with biopsy-proven LN ( = 45) and healthy controls ( = 20). LN chronicity index (CI) correlated with urinary exosomal miR-21, miR-150, and miR-29c (r = 0.565, 0.840, -0.559, respectively). This miRNA profile distinguished low CI from moderate-high CI in LN patients with a high sensitivity and specificity (94.4% and 99.8%). Furthermore, this multimarker panel predicted an increased risk of progression to end-stage renal disease (ESRD). Pathway analysis identified and as common target genes for the three miRNAs. Immunohistochemistry in LN renal biopsies revealed a significant increase of COL1A1 and COL4A1 correlated with renal chronicity. SP1 decreased significantly in the high-CI group ( = 0.002). VEGFA levels showed no differences. In vitro experiments suggest that these miRNA combinations promote renal fibrosis by increasing profibrotic molecules through SP1 and Smad3/TGFβ pathways. In conclusion, a urinary exosomal multimarker panel composed of miR-21, miR-150, and miR-29c provides a non-invasive method to detect early renal fibrosis and predict disease progression in LN.