title: Differential miRNA Expression in Cells and Matrix Vesicles in Vascular Smooth Muscle Cells from Rats with Kidney Disease.
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.
authors.affiliation: Department of Biohealth Informatics, School of Informatics and Computing, Indiana University Purdue University, Indianapolis, Indiana, United States of America.
authors.forename: Praneet
authors.initials: P
authors.lastname: Chaturvedi
authors.affiliation: Division of Nephrology, Department of Medicine, School of Medicine, Indiana University, Indianapolis, Indiana, United States of America.
authors.forename: Neal X
authors.initials: NX
authors.lastname: Chen
authors.affiliation: Division of Nephrology, Department of Medicine, School of Medicine, Indiana University, Indianapolis, Indiana, United States of America.
authors.forename: Kalisha
authors.initials: K
authors.lastname: O'Neill
authors.affiliation: Division of Nephrology, Department of Medicine, School of Medicine, Indiana University, Indianapolis, Indiana, United States of America.
authors.forename: Jeanette N
authors.initials: JN
authors.lastname: McClintick
authors.affiliation: Division of Nephrology, Department of Medicine, School of Medicine, Indiana University, Indianapolis, Indiana, United States of America; Roudebush VA Medical Center, Indianapolis, Indiana, United States of America.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Moe
authors.affiliation: Department of Biohealth Informatics, School of Informatics and Computing, Indiana University Purdue University, Indianapolis, Indiana, United States of America; Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, 5021 Health Information and Translational Sciences (HITS), Indianapolis, Indiana, United States of America; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Medical Research and Library Building, Indianapolis, Indiana, United States of America.
authors.forename: Sarath Chandra
authors.initials: SC
authors.lastname: Janga
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D005920:Glomerular Mesangium / Q000378:metabolism* / Q000473:pathology; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics*; D046228:Microarray Analysis; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D051436:Renal Insufficiency, Chronic / Q000235:genetics* / Q000473:pathology; D061205:Vascular Calcification / Q000235:genetics* / Q000378:metabolism
chemical_list: D035683:MicroRNAs