An Exosomal Urinary miRNA Signature for Early Diagnosis of Renal Fibrosis in Lupus Nephritis
Copyright policy )An Exosomal Urinary miRNA Signature for Early Diagnosis of Renal Fibrosis in Lupus Nephritis
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 (n = 45) and healthy controls (n = 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 VEGFA and SP1 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 (p = 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.
Adult, Male, ENFERMEDADES::enfermedades de la piel y tejido conjuntivo::enfermedades del tejido conjuntivo::lupus eritematoso sistémico::nefritis lúpica, Fibrosi, Biopsy, Exosomes, Real-Time Polymerase Chain Reaction, Article, Young Adult, Lupus eritematós sistèmic, DISEASES::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Fibrosis, Humans, DISEASES::Immune System Diseases::Autoimmune Diseases::Lupus Erythematosus, Systemic::Lupus Nephritis, lupus nephritis, multi-marker panel, MicroARN, COMPUESTOS QUÍMICOS Y DROGAS::nucleótidos y nucleósidos de ácidos nucleicos::nucleótidos y nucleósidos de ácidos nucleicos::ácidos nucleicos::nucleótidos y nucleósidos de ácidos nucleicos::ácidos nucleicos::ARN::nucleótidos y nucleósidos de ácidos nucleicos::ácidos nucleicos::ARN::ARN no traducido::ARN pequeño no traducido::microARN::microARN circulante, QH573-671, Gene Expression Profiling, Liquid Biopsy, renal fibrosis, Fibrosis, Immunohistochemistry, Lupus Nephritis, MicroRNAs, Early Diagnosis, ENFERMEDADES::afecciones patológicas, signos y síntomas::procesos patológicos::fibrosis, Female, CHEMICALS AND DRUGS::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Untranslated::RNA, Small Untranslated::MicroRNAs::Circulating MicroRNA, Cytology, urinary exosomes, Biomarkers
Adult, Male, ENFERMEDADES::enfermedades de la piel y tejido conjuntivo::enfermedades del tejido conjuntivo::lupus eritematoso sistémico::nefritis lúpica, Fibrosi, Biopsy, Exosomes, Real-Time Polymerase Chain Reaction, Article, Young Adult, Lupus eritematós sistèmic, DISEASES::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Fibrosis, Humans, DISEASES::Immune System Diseases::Autoimmune Diseases::Lupus Erythematosus, Systemic::Lupus Nephritis, lupus nephritis, multi-marker panel, MicroARN, COMPUESTOS QUÍMICOS Y DROGAS::nucleótidos y nucleósidos de ácidos nucleicos::nucleótidos y nucleósidos de ácidos nucleicos::ácidos nucleicos::nucleótidos y nucleósidos de ácidos nucleicos::ácidos nucleicos::ARN::nucleótidos y nucleósidos de ácidos nucleicos::ácidos nucleicos::ARN::ARN no traducido::ARN pequeño no traducido::microARN::microARN circulante, QH573-671, Gene Expression Profiling, Liquid Biopsy, renal fibrosis, Fibrosis, Immunohistochemistry, Lupus Nephritis, MicroRNAs, Early Diagnosis, ENFERMEDADES::afecciones patológicas, signos y síntomas::procesos patológicos::fibrosis, Female, CHEMICALS AND DRUGS::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Untranslated::RNA, Small Untranslated::MicroRNAs::Circulating MicroRNA, Cytology, urinary exosomes, Biomarkers
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