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Abnormal phenotypic switch, migration, and proliferation of vascular smooth muscle cells (VSMCs) are hallmarks for pathogenesis of thoracic aortic dissection (TAD). In the current study, we identified miR-134-5p as a critical regulator controlling human VSMC phenotypic switch and migration to investigate whether miR-134-5p affects human VSMC functions and development of TAD. Using miRNA microarray of aorta specimens from 12 TAD and 12 controls, we identified miR-134-5p, which was significantly downregulated in TAD tissues. With qPCR detection, we found that miR-134-5p was also evidently decreased in human AoSMCs. Ectopic expression of miR-134-5p obviously promoted VSMC differentiation and expression of contractile markers, such as α-SMA, SM22α, and MYH11. miR-134-5p potently inhibited PDGF-BB-induced VSMC phenotypic switch and migration. We further identified STAT5B and ITGB1 as downstream targets of miR-134-5p in human VSMCs and proved them to be mediators in VSMC phenotypic switch and progression of TAD. Finally, Ad-miR-134-5p obviously suppressed the aorta dilatation and vascular media degeneration by 39% in TAD mice after vascular injury induced by Ang II. Our findings revealed that miR-134-5p was a novel regulator in vascular remodeling and pathological progress of TAD via targeting STAT5B/ITGB1 expression. Targeting miR-134-5p or its downstream molecules in VSMCs might develop new avenues in clinical treatment of TAD.
Pubmed ID: 30951965
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Commercial organization which provides reagents and services for molecular biology research. Its services include clone collections, microRNA solutions, genome editing, qPCR products, and fluorescent labeling and detection.
View all literature mentionsCommercial organization for research and development genomics services and technical support to researchers.
View all literature mentionsDatabase of microRNA target predictions and expression profiles. Target predictions are based on a development of the miRanda algorithm which incorporates current biological knowledge on target rules and on the use of an up-to-date compendium of mammalian microRNAs. MicroRNA expression profiles are derived from a comprehensive sequencing project of a large set of mammalian tissues and cell lines of normal and disease origin. This website enables users to explore: * The set of genes that are potentially regulated by a particular microRNA. * The implied cooperativity of multiple microRNAs on a particular mRNA. * MicroRNA expression profiles in various mammalian tissues. The web resource provides users with functional information about the growing number of microRNAs and their interaction with target genes in many species and facilitates novel discoveries in microRNA gene regulation. The microRNA Target Detection Software, miRanda, is an algorithm for finding genomic targets for microRNAs. This algorithm has been written in C and is available as an open-source method under the GPL.
View all literature mentionsWeb tool to predict biological targets of miRNAs by searching for presence of conserved 8mer, 7mer and 6mer sites that match seed region of each miRNA. Nonconserved sites are also predicted and sites with mismatches in seed region that are compensated by conserved 3' pairing. Used to search for predicted microRNA targets in mammals.
View all literature mentionsCatalogs of predicted microRNA targets in worm (based on ce6 genome assembly), fly (dm3), mouse (mm9) and human (hg18). We follow standard seed parameter settings and consider seeds of length 6-8 bases, beginning at position 2 of the microRNA. No mismatches or loops are allowed, but a single G:U wobble is allowed in 7- or 8-mers. In genes missing a 3' UTR annotation, 500 bp (fly), 800 bp (human and mouse) or 300 bp (worm) downstream of the annotated end of the coding sequence were used as the predicted UTR. For each organism, a catalog with zero flank and with a flank of 3 and 15 bases upstream and downstream.
View all literature mentionsIntegrated database resource consisting of 16 main databases, broadly categorized into systems information, genomic information, and chemical information. In particular, gene catalogs in completely sequenced genomes are linked to higher-level systemic functions of cell, organism, and ecosystem. Analysis tools are also available. KEGG may be used as reference knowledge base for biological interpretation of large-scale datasets generated by sequencing and other high-throughput experimental technologies.
View all literature mentionsA commercial antibody supplier which supplies primary and secondary antibodies, biochemicals, proteins, peptides, lysates, immunoassays and other kits.
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