Differential miRNA expression in cells and matrix vesicles in vascular smooth muscle cells from rats with kidney disease

Praneet Chaturvedi, Xuening (Neal) Chen, Kalisha O'Neill, Jeanette McClintick, Sharon Moe, Sarath Chandra Janga

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Article numbere0131589
JournalPLoS One
Volume10
Issue number6
DOIs
StatePublished - Jun 26 2015

Fingerprint

Kidney Diseases
kidney diseases
MicroRNAs
microRNA
Vascular Smooth Muscle
blood vessels
smooth muscle
myocytes
Smooth Muscle Myocytes
Muscle
Rats
Cells
rats
calcification
Vascular Calcification
cells
Chronic Renal Insufficiency
Gene Regulatory Networks
Microarrays
Genes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Differential miRNA expression in cells and matrix vesicles in vascular smooth muscle cells from rats with kidney disease. / Chaturvedi, Praneet; Chen, Xuening (Neal); O'Neill, Kalisha; McClintick, Jeanette; Moe, Sharon; Janga, Sarath Chandra.

In: PLoS One, Vol. 10, No. 6, e0131589, 26.06.2015.

Research output: Contribution to journalArticle

Chaturvedi, Praneet ; Chen, Xuening (Neal) ; O'Neill, Kalisha ; McClintick, Jeanette ; Moe, Sharon ; Janga, Sarath Chandra. / Differential miRNA expression in cells and matrix vesicles in vascular smooth muscle cells from rats with kidney disease. In: PLoS One. 2015 ; Vol. 10, No. 6.
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