Parallel Analysis of mRNA and microRNA Microarray Profiles to Explore Functional Regulatory Patterns in Polycystic Kidney Disease: Using PKD/Mhm Rat Model

Autosomal polycystic kidney disease (ADPKD) is a frequent monogenic renal disease, characterised by fluid-filled cysts that are thought to result from multiple deregulated pathways such as cell proliferation and apoptosis. MicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression of...

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Vydané v:PloS one Ročník 8; číslo 1; s. e53780
Hlavní autori: Dweep, Harsh, Sticht, Carsten, Kharkar, Asawari, Pandey, Priyanka, Gretz, Norbert
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States Public Library of Science 10.01.2013
Public Library of Science (PLoS)
Predmet:
Animal models
Animals
Apoptosis
Aquaporins
Binding sites
Biological activity
Biology
Cell cycle
Cell growth
Cell proliferation
Cysts
Deoxyribonucleic acid
Deregulation
Disease Models, Animal
DNA
DNA biosynthesis
DNA microarrays
DNA replication
Epidemiology
Extracellular matrix
Fibrosis
Fluids
Gene expression
Gene Expression Profiling
Genes
Genetic aspects
Genomics
Humans
Kidney diseases
Kidney transplantation
Kidneys
Medical research
Medicine
Messenger RNA
Metabolic Networks and Pathways - genetics
Metabolic pathways
Metabolism
Microarray Analysis
MicroRNA
MicroRNAs
MicroRNAs - genetics
miRNA
mRNA
Pathogenesis
Polycystic kidney
Polycystic kidney disease
Polycystic Kidney Diseases - genetics
Polycystic Kidney Diseases - pathology
Rats
Ribonucleic acid
RNA
RNA, Messenger - genetics
Rodents
Signal transduction
Signal Transduction - genetics
Signaling
Transforming growth factors
Up-Regulation
Wnt protein
ISSN:1932-6203, 1932-6203
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Popis
Shrnutí:Autosomal polycystic kidney disease (ADPKD) is a frequent monogenic renal disease, characterised by fluid-filled cysts that are thought to result from multiple deregulated pathways such as cell proliferation and apoptosis. MicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression of many genes associated with such biological processes and human pathologies. To explore the possible regulatory role of miRNAs in PKD, the PKD/Mhm (cy/+) rat, served as a model to study human ADPKD. A parallel microarray-based approach was conducted to profile the expression changes of mRNAs and miRNAs in PKD/Mhm rats. 1,573 up- and 1,760 down-regulated genes were differentially expressed in PKD/Mhm. These genes are associated with 17 pathways (such as focal adhesion, cell cycle, ECM-receptor interaction, DNA replication and metabolic pathways) and 47 (e.g., cell proliferation, Wnt and Tgfβ signaling) Gene Ontologies. Furthermore, we found the similar expression patterns of deregulated genes between PKD/Mhm (cy/+) rat and human ADPKD, PKD1(L3/L3), PKD1(-/-), Hnf1α-deficient, and Glis2(lacZ/lacZ) models. Additionally, several differentially regulated genes were noted to be target hubs for miRNAs. We also obtained 8 significantly up-regulated miRNAs (rno-miR-199a-5p, -214, -146b, -21, -34a, -132, -31 and -503) in diseased kidneys of PKD/Mhm rats. Additionally, the binding site overrepresentation and pathway enrichment analyses were accomplished on the putative targets of these 8 miRNAs. 7 out of these 8 miRNAs and their possible interactions have not been previously described in ADPKD. We have shown a strong overlap of functional patterns (pathways) between deregulated miRNAs and mRNAs in the PKD/Mhm (cy/+) rat model. Our findings suggest that several miRNAs may be associated in regulating pathways in ADPKD. We further describe novel miRNAs and their possible targets in ADPKD, which will open new avenues to understand the pathogenesis of human ADPKD. Furthermore they could serve as a useful resource for anti-fibrotic therapeutics.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
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Competing Interests: The authors have declared that no competing interests exist.
Conceived and designed the experiments: HD NG. Performed the experiments: HD. Analyzed the data: HD CS AK PP. Wrote the paper: HD NG.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0053780