title: Renal microRNA- and RNA-profiles in progressive chronic kidney disease.
abstract: BACKGROUND
  MicroRNAs (miRNAs) contribute to chronic kidney disease (CKD) progression via regulating mRNAs involved in renal homeostasis. However, their association with clinical outcome remains poorly understood.
  
  
  METHODS
  We performed miRNA and mRNA expression profiling on renal biopsy sections by qPCR (miRNA) and microarrays (mRNA) in a discovery (n = 43) and in a validation (n = 29) cohort. miRNAs differentiating stable and progressive cases were inversely correlated with putative target mRNAs, which were further characterized by pathway analysis using KEGG pathways.
  
  
  RESULTS
  miR-30d, miR-140-3p, miR-532-3p, miR-194, miR-190, miR-204 and miR-206 were downregulated in progressive cases. These seven miRNAs correlated with upregulated 29 target mRNAs involved in inflammatory response, cell-cell interaction, apoptosis and intra-cellular signalling. In particular, miR-206 and miR-532-3p were associated with distinct biological processes via the expression of their target mRNAs: Reduced expression of miR-206 in progressive disease correlated with the upregulation of target mRNAs participating in inflammatory pathways (CCL19, CXCL1, IFNAR2, NCK2, PTK2B, PTPRC, RASGRP1 and TNFRSF25). Progressive cases also showed a lower expression of miR-532-3p and an increased expression of target transcripts involved in apoptosis pathways (MAP3K14, TNFRSF10B/TRAIL-R2, TRADD and TRAF2). In the validation cohort, we confirmed the decreased expression of miR-206 and miR-532-3p, and the inverse correlation of these miRNAs with the expression of nine of the 12 target genes. The levels of the identified miRNAs and the target mRNAs correlated with clinical parameters and histological damage indices.
  
  
  CONCLUSIONS
  These results suggest the involvement of specific miRNAs and mRNAs in biological pathways associated with the progression of CKD.
authors.affiliation: Department of Internal Medicine IV - Nephrology and Hypertension, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Rudnicki
authors.affiliation: Emergentec Biodevelopment GmbH, Vienna, Austria.
authors.forename: Paul
authors.initials: P
authors.lastname: Perco
authors.affiliation: Biogazelle, Zwijnaarde, Belgium.
authors.forename: Barbara
authors.initials: B
authors.lastname: D Haene
authors.affiliation: Department of Internal Medicine IV - Nephrology and Hypertension, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Leierer
authors.affiliation: Emergentec Biodevelopment GmbH, Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Heinzel
authors.affiliation: Emergentec Biodevelopment GmbH, Vienna, Austria.
authors.forename: Irmgard
authors.initials: I
authors.lastname: Mühlberger
authors.affiliation: Department of Internal Medicine IV - Nephrology and Hypertension, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Ninella
authors.initials: N
authors.lastname: Schweibert
authors.affiliation: Department of Internal Medicine IV - Nephrology and Hypertension, Medical University Innsbruck, Innsbruck, Austria.|Department of Nephrology, KH Elisabethinen, Linz, Austria.
authors.forename: Judith
authors.initials: J
authors.lastname: Sunzenauer
authors.affiliation: Institute of Pathology, Medical University Vienna, Vienna, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Regele
authors.affiliation: Department of Internal Medicine IV - Nephrology and Hypertension, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Andreas
authors.identifier: http://orcid.org/0000-0002-2945-2946
authors.initials: A
authors.lastname: Kronbichler
authors.affiliation: Biogazelle, Zwijnaarde, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Mestdagh
authors.affiliation: Biogazelle, Zwijnaarde, Belgium.
authors.forename: Jo
authors.initials: J
authors.lastname: Vandesompele
authors.affiliation: Emergentec Biodevelopment GmbH, Vienna, Austria.
authors.forename: Bernd
authors.initials: B
authors.lastname: Mayer
authors.affiliation: Department of Internal Medicine IV - Nephrology and Hypertension, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Gert
authors.initials: G
authors.lastname: Mayer
mesh_terms: D000328:Adult; D000368:Aged; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000235:genetics / Q000378:metabolism; D015331:Cohort Studies; D003928:Diabetic Nephropathies / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D005922:Glomerulonephritis, IGA / Q000235:genetics / Q000378:metabolism; D015432:Glomerulonephritis, Membranoproliferative / Q000235:genetics / Q000378:metabolism; D015433:Glomerulonephritis, Membranous / Q000235:genetics / Q000378:metabolism; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008181:Lupus Nephritis / Q000235:genetics / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009400:Nephrosclerosis / Q000235:genetics / Q000378:metabolism; D009402:Nephrosis, Lipoid / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D051436:Renal Insufficiency, Chronic / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger
keywords: Biomarker; chronic kidney disease; miRNA; microarray; systems biology; transcriptomics