1. Extracellular microRNA signature in chronic kidney disease
- Author
-
Jagdeesan Muralidharan, Srinivasan Beddhu, Jeffrey B. Kopp, Dominic S. Raj, Savas Ozturk, Susan Knoblach, Shashi Shrivastav, Ali Ramezani, Monica J. Hubal, Richard Scott, Sara Karandish, and Nirmal Maxwell
- Subjects
0301 basic medicine ,Adult ,Genetic Markers ,Male ,Physiology ,Mice, Transgenic ,Biology ,Bioinformatics ,Kidney ,Cell Line ,Transcriptome ,Transforming Growth Factor beta1 ,03 medical and health sciences ,Transforming Growth Factor beta ,Albumins ,Gene expression ,microRNA ,medicine ,Extracellular ,Animals ,Humans ,Gene Regulatory Networks ,Genetic Predisposition to Disease ,Renal Insufficiency, Chronic ,Aged ,Oligonucleotide Array Sequence Analysis ,Gene Expression Profiling ,Transforming growth factor beta ,Middle Aged ,medicine.disease ,Fibrosis ,Rats ,Gene expression profiling ,Mice, Inbred C57BL ,Disease Models, Animal ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,Phenotype ,Cancer research ,biology.protein ,Mice, Inbred CBA ,Female ,Kidney disease ,Research Article ,Glomerular Filtration Rate - 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. −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
- Published
- 2017