RGD Reference Report - MicroRNA-21 regulates peroxisome proliferator-activated receptor alpha, a molecular mechanism of cardiac pathology in Cardiorenal Syndrome Type 4. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

MicroRNA-21 regulates peroxisome proliferator-activated receptor alpha, a molecular mechanism of cardiac pathology in Cardiorenal Syndrome Type 4.

Authors: Chuppa, Sandra  Liang, Mingyu  Liu, Pengyuan  Liu, Yong  Casati, Marc C  Cowley, Allen W  Patullo, Leah  Kriegel, Alison J 
Citation: Chuppa S, etal., Kidney Int. 2018 Feb;93(2):375-389. doi: 10.1016/j.kint.2017.05.014. Epub 2017 Jul 29.
RGD ID: 41410821
Pubmed: PMID:28760335   (View Abstract at PubMed)
PMCID: PMC5787401   (View Article at PubMed Central)
DOI: DOI:10.1016/j.kint.2017.05.014   (Journal Full-text)

Cardiovascular events are the leading cause of death in patients with chronic kidney disease (CKD), although the pathological mechanisms are poorly understood. Here we longitudinally characterized left ventricle pathology in a 5/6 nephrectomy rat model of CKD and identify novel molecular mediators. Next-generation sequencing of left ventricle mRNA and microRNA (miRNA) was performed at physiologically distinct points in disease progression, identifying alterations in genes in numerous immune, lipid metabolism, and inflammatory pathways, as well as several miRNAs. MiRNA miR-21-5p was increased in our dataset and has been reported to regulate many identified pathways. Suppression of miR-21-5p protected rats with 5/6 nephrectomy from developing left ventricle hypertrophy and improved left ventricle function. Next-generation mRNA sequencing revealed that miR-21-5p suppression altered gene expression in peroxisome proliferator-activated receptor alpha (PPARα) regulated pathways in the left ventricle. PPARα, a miR-21-5p target, is the primary PPAR isoform in the heart, importantly involved in regulating fatty acid metabolism. Therapeutic delivery of low-dose PPARα agonist (clofibrate) to rats with 5/6 nephrectomy improved cardiac function and prevented left ventricle dilation. Thus, comprehensive characterization of left ventricle molecular changes highlights the involvement of numerous signaling pathways not previously explored in CKD models and identified PPARα as a potential therapeutic target for CKD-related cardiac dysfunction.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Cardio-Renal Syndrome amelioratesISOMir21 (Rattus norvegicus)41410821; 41410821 RGD 
Cardio-Renal Syndrome amelioratesIMP 41410821 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mir21  (microRNA 21)

Genes (Mus musculus)
Mir21a  (microRNA 21a)

Genes (Homo sapiens)
MIR21  (microRNA 21)


Additional Information