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Differential miRNA Expression in Cells and Matrix Vesicles in Vascular Smooth Muscle Cells from Rats with Kidney Disease.

Chaturvedi P, Chen NX, O'Neill K, McClintick JN, Moe SM, Janga SC - PLoS ONE (2015)

Bottom Line: The percentage of miRNA to total RNA was increased in MV compared to VSMC.We found several processes including vascular smooth muscle contraction, response to hypoxia and regulation of muscle cell differentiation to be enriched.In conclusion, our results demonstrate that miRs are concentrated in MV from calcifying VSMC, and that important functions and pathways are affected by the miRs dysregulation between calcifying VSMC and the MV they produce.

View Article: PubMed Central - PubMed

Affiliation: Department of Biohealth Informatics, School of Informatics and Computing, Indiana University Purdue University, Indianapolis, Indiana, United States of America.

ABSTRACT
Vascular calcification is a complex process and has been associated with aging, diabetes, chronic kidney disease (CKD). Although there have been several studies that examine the role of miRNAs (miRs) in bone osteogenesis, little is known about the role of miRs in vascular calcification and their role in the pathogenesis of vascular abnormalities. Matrix vesicles (MV) are known to play in important role in initiating vascular smooth muscle cell (VSMC) calcification. In the present study, we performed miRNA microarray analysis to identify the dysregulated miRs between MV and VSMC derived from CKD rats to understand the role of post-transcriptional regulatory networks governed by these miRNAs in vascular calcification and to uncover the differential miRNA content of MV. The percentage of miRNA to total RNA was increased in MV compared to VSMC. Comparison of expression profiles of miRNA by microarray demonstrated 33 miRs to be differentially expressed with the majority (~ 57%) of them down-regulated. Target genes controlled by differentially expressed miRNAs were identified utilizing two different complementary computational approaches Miranda and Targetscan to understand the functions and pathways that may be affected due to the production of MV from calcifying VSMC thereby contributing to the regulation of genes by miRs. We found several processes including vascular smooth muscle contraction, response to hypoxia and regulation of muscle cell differentiation to be enriched. Signaling pathways identified included MAP-kinase and wnt signaling that have previously been shown to be important in vascular calcification. In conclusion, our results demonstrate that miRs are concentrated in MV from calcifying VSMC, and that important functions and pathways are affected by the miRs dysregulation between calcifying VSMC and the MV they produce. This suggests that miRs may play a very important regulatory role in vascular calcification in CKD by controlling an extensive network of post-transcriptional targets.

No MeSH data available.


Related in: MedlinePlus

Enrichment of biological functions in the gene set controlled by at least 3 miRs using ClueGo.Analyses of those genese controlled by at least three miRNA were performed to identify important pathways. The genes were categorized based on ClueGo, a plugin of the cytoscape and all the functions reported are at p-value < = 0.05. The size of the nodes represents the number of miRNAs that regulate the genes, and the connectivity of multiple miRNAs regulating multiple genes within a common pathway are shown by the black lines. Purine biosynthesis and cAMP regulation demonstrated the most miRNA regulation (purple nodes).
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pone.0131589.g006: Enrichment of biological functions in the gene set controlled by at least 3 miRs using ClueGo.Analyses of those genese controlled by at least three miRNA were performed to identify important pathways. The genes were categorized based on ClueGo, a plugin of the cytoscape and all the functions reported are at p-value < = 0.05. The size of the nodes represents the number of miRNAs that regulate the genes, and the connectivity of multiple miRNAs regulating multiple genes within a common pathway are shown by the black lines. Purine biosynthesis and cAMP regulation demonstrated the most miRNA regulation (purple nodes).

Mentions: We performed functional and pathway enrichment for the genes controlled by at least 3 miRs using ClueGo—a plugin in Cytoscape [14] and David—a functional/pathway enrichment tool [15, 16]. We obtained orthologs of genes controlled by at least 3 miRs in mouse as ClueGo is not capable of handling the rat genome and visualized the network of functions obtained at p-value < = 0.05 (Fig 6). Further, we also performed functional and pathway enrichment of the genes using David with the background species set to rat (rattus novergicus) at a p-value < = 0.01 and FDR = 5% (see S1 Fig and S3 Table). The results demonstrated several important pathways and functions to be associated with the genes controlled by multiple dysregulated miRs between VSMC and MV.


Differential miRNA Expression in Cells and Matrix Vesicles in Vascular Smooth Muscle Cells from Rats with Kidney Disease.

Chaturvedi P, Chen NX, O'Neill K, McClintick JN, Moe SM, Janga SC - PLoS ONE (2015)

Enrichment of biological functions in the gene set controlled by at least 3 miRs using ClueGo.Analyses of those genese controlled by at least three miRNA were performed to identify important pathways. The genes were categorized based on ClueGo, a plugin of the cytoscape and all the functions reported are at p-value < = 0.05. The size of the nodes represents the number of miRNAs that regulate the genes, and the connectivity of multiple miRNAs regulating multiple genes within a common pathway are shown by the black lines. Purine biosynthesis and cAMP regulation demonstrated the most miRNA regulation (purple nodes).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4482652&req=5

pone.0131589.g006: Enrichment of biological functions in the gene set controlled by at least 3 miRs using ClueGo.Analyses of those genese controlled by at least three miRNA were performed to identify important pathways. The genes were categorized based on ClueGo, a plugin of the cytoscape and all the functions reported are at p-value < = 0.05. The size of the nodes represents the number of miRNAs that regulate the genes, and the connectivity of multiple miRNAs regulating multiple genes within a common pathway are shown by the black lines. Purine biosynthesis and cAMP regulation demonstrated the most miRNA regulation (purple nodes).
Mentions: We performed functional and pathway enrichment for the genes controlled by at least 3 miRs using ClueGo—a plugin in Cytoscape [14] and David—a functional/pathway enrichment tool [15, 16]. We obtained orthologs of genes controlled by at least 3 miRs in mouse as ClueGo is not capable of handling the rat genome and visualized the network of functions obtained at p-value < = 0.05 (Fig 6). Further, we also performed functional and pathway enrichment of the genes using David with the background species set to rat (rattus novergicus) at a p-value < = 0.01 and FDR = 5% (see S1 Fig and S3 Table). The results demonstrated several important pathways and functions to be associated with the genes controlled by multiple dysregulated miRs between VSMC and MV.

Bottom Line: The percentage of miRNA to total RNA was increased in MV compared to VSMC.We found several processes including vascular smooth muscle contraction, response to hypoxia and regulation of muscle cell differentiation to be enriched.In conclusion, our results demonstrate that miRs are concentrated in MV from calcifying VSMC, and that important functions and pathways are affected by the miRs dysregulation between calcifying VSMC and the MV they produce.

View Article: PubMed Central - PubMed

Affiliation: Department of Biohealth Informatics, School of Informatics and Computing, Indiana University Purdue University, Indianapolis, Indiana, United States of America.

ABSTRACT
Vascular calcification is a complex process and has been associated with aging, diabetes, chronic kidney disease (CKD). Although there have been several studies that examine the role of miRNAs (miRs) in bone osteogenesis, little is known about the role of miRs in vascular calcification and their role in the pathogenesis of vascular abnormalities. Matrix vesicles (MV) are known to play in important role in initiating vascular smooth muscle cell (VSMC) calcification. In the present study, we performed miRNA microarray analysis to identify the dysregulated miRs between MV and VSMC derived from CKD rats to understand the role of post-transcriptional regulatory networks governed by these miRNAs in vascular calcification and to uncover the differential miRNA content of MV. The percentage of miRNA to total RNA was increased in MV compared to VSMC. Comparison of expression profiles of miRNA by microarray demonstrated 33 miRs to be differentially expressed with the majority (~ 57%) of them down-regulated. Target genes controlled by differentially expressed miRNAs were identified utilizing two different complementary computational approaches Miranda and Targetscan to understand the functions and pathways that may be affected due to the production of MV from calcifying VSMC thereby contributing to the regulation of genes by miRs. We found several processes including vascular smooth muscle contraction, response to hypoxia and regulation of muscle cell differentiation to be enriched. Signaling pathways identified included MAP-kinase and wnt signaling that have previously been shown to be important in vascular calcification. In conclusion, our results demonstrate that miRs are concentrated in MV from calcifying VSMC, and that important functions and pathways are affected by the miRs dysregulation between calcifying VSMC and the MV they produce. This suggests that miRs may play a very important regulatory role in vascular calcification in CKD by controlling an extensive network of post-transcriptional targets.

No MeSH data available.


Related in: MedlinePlus