title: Urinary Exosomes Contain MicroRNAs Capable of Paracrine Modulation of Tubular Transporters in Kidney.
abstract: Exosomes derived from all nephron segments are present in human urine, where their functionality is incompletely understood. Most studies have focused on biomarker discovery rather than exosome function. Through sequencing we identified the miRNA repertoire of urinary exosomes from healthy volunteers; 276 mature miRNAs and 345 pre-miRNAs were identified (43%/7% of reads). Among the most abundant were members of the miR-10, miR-30 and let-7 families. Targets for the identified miRNAs were predicted using five different databases; genes encoding membrane transporters and their regulators were enriched, highlighting the possibility that these miRNAs could modulate key renal tubular functions in a paracrine manner. As proof of concept, cultured renal epithelial cells were exposed to urinary exosomes and cellular exosomal uptake was confirmed; thereafter, reduced levels of the potassium channel ROMK and kinases SGK1 and WNK1 were observed in a human collecting duct cell line, while SPAK was unaltered. In proximal tubular cells, mRNA levels of the amino acid transporter gene SLC38A2 were diminished and reflected in a significant decrement of its encoded protein SNAT2. Protein levels of the kinase SGK1 did not change. Thus we demonstrated a novel potential function for miRNA in urinary exosomes.
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
authors.forename: Tannia
authors.initials: T
authors.lastname: Gracia
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge, UK.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
authors.forename: Ya
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Norgett
authors.affiliation: Department of Veterinary Medicine University of Cambridge, Cambridge, UK.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Williams
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
authors.forename: Pablo
authors.initials: P
authors.lastname: Moreno
authors.affiliation: Departments of Genetic, University of Cambridge, Cambridge, UK.
authors.forename: Gos
authors.initials: G
authors.lastname: Micklem
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
authors.forename: Fiona E
authors.initials: FE
authors.lastname: Karet Frankl
mesh_terms: D000328:Adult; D001692:Biological Transport; D004847:Epithelial Cells / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism*; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D019899:Paracrine Communication; D015203:Reproducibility of Results; D059467:Transcriptome
chemical_list: D035683:MicroRNAs