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Am J Physiol Renal Physiol. 2017 Jun 1;312(6):F982-F991. doi: 10.1152/ajprenal.00569.2016. Epub 2017 Jan 11.

Extracellular microRNA signature in chronic kidney disease.

Author information

1
Division of Renal Diseases and Hypertension, The George Washington University School of Medicine, Washington, District of Columbia.
2
Department of Exercise and Nutrition Sciences, George Washington University, Washington, District of Columbia.
3
Center for Genetic Medicine Research, Children's National Medical Center, Washington, District of Columbia.
4
Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
5
College of Veterinary Medicine, Western University of Health Sciences, Pomona, California.
6
University of Florida, School of Medicine, Miami, Florida.
7
Department of Nephrology, Haseki Training and Research Hospital, Istanbul, Turkey; and.
8
Division of Nephrology, University of Utah School of Medicine, Salt Lake City, Utah.
9
Division of Renal Diseases and Hypertension, The George Washington University School of Medicine, Washington, District of Columbia; draj@mfa.gwu.edu.

Abstract

MicroRNAs (miRNAs) are noncoding RNAs that regulate posttranscriptional gene expression. In this study we characterized the circulating and urinary miRNA pattern associated with reduced glomerular filtration rate, using Affymetrix GeneChip miR 4.0 in 28 patients with chronic kidney disease (CKD). Top miRNA discoveries from the human studies were validated in an Alb/TGFβ mouse model of CKD, and in rat renal proximal tubular cells (NRK52E) exposed to TGFβ1. Plasma and urinary levels of procollagen III N-terminal propeptide and collagen IV were elevated in patients with decreased estimated glomerular filtration rate (eGFR). Expression of 384 urinary and 266 circulatory miRNAs were significantly different between CKD patients with eGFR ≥30 vs. <30 ml·min-1·1.73 m-2 Pathway analysis mapped multiple miRNAs to TGFβ signaling-related mRNA targets. Specifically, Let-7a was significantly downregulated, and miR-130a was significantly upregulated, in urine of patients with eGFR <30; miR-1825 and miR-1281 were upregulated in both urine and plasma of patients with decreased eGFR; and miR-423 was significantly downregulated in plasma of patients with decreased eGFR. miRNA expression in urine and plasma of Alb/TGFβ mice generally resembled and confirmed most, although not all, of the observations from the human studies. In response to TGFβ1 exposure, rat renal proximal tubular cells overexpressed miR-1825 and downregulated miR-423. Thus, miRNA are associated with kidney fibrosis, and specific urinary and plasma miRNA profile may have diagnostic and prognostic utility in CKD.

KEYWORDS:

TGFβ; chronic kidney disease; fibrosis

PMID:
28077372
PMCID:
PMC5495885
DOI:
10.1152/ajprenal.00569.2016
[Indexed for MEDLINE]
Free PMC Article

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