Role of microRNA 1207-5P and its host gene, the long non-coding RNA Pvt1, as mediators of extracellular matrix accumulation in the kidney: implications for diabetic nephropathy

Diabetic nephropathy is the most common cause of chronic kidney failure and end-stage renal disease in the Western World. One of the major characteristics of this disease is the excessive accumulation of extracellular matrix (ECM) in the kidney glomeruli. While both environmental and genetic determi...

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Bibliographic Details
Published in:PloS one 2013-10, Vol.8 (10), p.e77468-e77468
Main Authors: Alvarez, M Lucrecia, Khosroheidari, Mahdieh, Eddy, Elena, Kiefer, Jeff
Format: Article
Language:English
Subjects:
Accumulation
Binding sites
Cells, Cultured
Chromosome 5
Deoxyribonucleic acid
Diabetes
Diabetes mellitus
Diabetic Nephropathies - genetics
Diabetic Nephropathies - metabolism
Diabetic Nephropathies - pathology
Diabetic nephropathy
DNA
DNA methylation
End-stage renal disease
Epigenetics
Epithelial Cells - cytology
Epithelial Cells - drug effects
Epithelial Cells - metabolism
Extracellular matrix
Extracellular Matrix - metabolism
Extracellular Matrix - pathology
Fibronectin
Fibronectins - genetics
Fibronectins - metabolism
Gene expression
Gene Expression Regulation
Genomics
Glucose
Glucose - pharmacology
Growth factors
Humans
Kidney diseases
Kidney Tubules, Proximal - metabolism
Kidney Tubules, Proximal - pathology
Kinases
Mesangial cells
Mesangial Cells - cytology
Mesangial Cells - drug effects
Mesangial Cells - metabolism
Metabolic disorders
MicroRNAs
MicroRNAs - genetics
MicroRNAs - metabolism
miRNA
Nephropathy
Non-coding RNA
Pathogenesis
Plasmacytoma
Plasminogen Activator Inhibitor 1 - genetics
Plasminogen Activator Inhibitor 1 - metabolism
Plasminogen activator inhibitors
Polyamide-imides
Proteins
Proteins - genetics
Proteins - metabolism
Regulation
Renal failure
Ribonucleic acid
RNA
RNA, Long Noncoding
Rodents
Signal Transduction
Studies
Transforming Growth Factor beta1 - genetics
Transforming Growth Factor beta1 - metabolism
Transforming Growth Factor beta1 - pharmacology
Transforming growth factor-b1
Translocation
Ultrasonic imaging
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Summary:Diabetic nephropathy is the most common cause of chronic kidney failure and end-stage renal disease in the Western World. One of the major characteristics of this disease is the excessive accumulation of extracellular matrix (ECM) in the kidney glomeruli. While both environmental and genetic determinants are recognized for their role in the development of diabetic nephropathy, epigenetic factors, such as DNA methylation, long non-coding RNAs, and microRNAs, have also recently been found to underlie some of the biological mechanisms, including ECM accumulation, leading to the disease. We previously found that a long non-coding RNA, the plasmacytoma variant translocation 1 (PVT1), increases plasminogen activator inhibitor 1 (PAI-1) and transforming growth factor beta 1 (TGF-β1) in mesangial cells, the two main contributors to ECM accumulation in the glomeruli under hyperglycemic conditions, as well as fibronectin 1 (FN1), a major ECM component. Here, we report that miR-1207-5p, a PVT1-derived microRNA, is abundantly expressed in kidney cells, and is upregulated by glucose and TGF-β1. We also found that like PVT1, miR-1207-5p increases expression of TGF-β1, PAI-1, and FN1 but in a manner that is independent of its host gene. In addition, regulation of miR-1207-5p expression by glucose and TGFβ1 is independent of PVT1. These results provide evidence supporting important roles for miR-1207-5p and its host gene in the complex pathogenesis of diabetic nephropathy.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0077468