title: Urinary Exosomal miRNA Signature in Type II Diabetic Nephropathy Patients.
abstract: MicroRNAs (miRNAs) are short non-coding RNA species which are important post-transcriptional regulators of gene expression and play an important role in the pathogenesis of diabetic nephropathy. miRNAs are present in urine in a remarkably stable form packaged in extracellular vesicles, predominantly exosomes. In the present study, urinary exosomal miRNA profiling was conducted in urinary exosomes obtained from 8 healthy controls (C), 8 patients with type II diabetes (T2D) and 8 patients with type II diabetic nephropathy (DN) using Agilent´s miRNA microarrays. In total, the expression of 16 miRNA species was deregulated (>2-fold) in DN patients compared to healthy donors and T2D patients: the expression of 14 miRNAs (miR-320c, miR-6068, miR-1234-5p, miR-6133, miR-4270, miR-4739, miR-371b-5p, miR-638, miR-572, miR-1227-5p, miR-6126, miR-1915-5p, miR-4778-5p and miR-2861) was up-regulated whereas the expression of 2 miRNAs (miR-30d-5p and miR-30e-5p) was down-regulated. Most of the deregulated miRNAs are involved in progression of renal diseases. Deregulation of urinary exosomal miRNAs occurred in micro-albuminuric DN patients but not in normo-albuminuric DN patients. We used qRT-PCR based analysis of the most strongly up-regulated miRNAs in urinary exosomes from DN patients, miRNAs miR-320c and miR-6068. The correlation of miRNA expression and micro-albuminuria levels could be replicated in a confirmation cohort. In conclusion, urinary exosomal miRNA content is altered in type II diabetic patients with DN. Deregulated miR-320c, which might have an impact on the TGF-β-signaling pathway via targeting thrombospondin 1 (TSP-1) shows promise as a novel candidate marker for disease progression in type II DN that should be evaluated in future studies.
authors.affiliation: Translational Medicine & Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorferstr.65, 88397 Biberach, Germany.
authors.forename: Denis
authors.initials: D
authors.lastname: Delić
authors.affiliation: Translational Medicine & Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorferstr.65, 88397 Biberach, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Eisele
authors.affiliation: Translational Medicine & Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorferstr.65, 88397 Biberach, Germany.
authors.forename: Ramona
authors.initials: R
authors.lastname: Schmid
authors.affiliation: Translational Medicine & Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorferstr.65, 88397 Biberach, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Baum
authors.affiliation: Translational Medicine & Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorferstr.65, 88397 Biberach, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Wiech
authors.affiliation: Translational Medicine & Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorferstr.65, 88397 Biberach, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Gerl
authors.affiliation: R&D Project Management, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorferstr.65, 88397 Biberach, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Zimdahl
authors.affiliation: Cardiometabolic Diseases Research, Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, Connecticut 06877-0368, United States of America.
authors.forename: Steven S
authors.initials: SS
authors.lastname: Pullen
authors.affiliation: Translational Medicine & Clinical Pharmacology, Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, Connecticut 06877-0368, United States of America.
authors.forename: Richard
authors.initials: R
authors.lastname: Urquhart
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D003928:Diabetic Nephropathies / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D055354:Exosomes / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000652:urine*; D008875:Middle Aged; D015398:Signal Transduction / Q000502:physiology; D055815:Young Adult
chemical_list: D035683:MicroRNAs