miR-145-5p Inhibits Vascular Smooth Muscle Cells (VSMCs) Proliferation and Migration by Dysregulating the Transforming Growth Factor-β Signaling Cascade
| Autor: | Li Li, Ming Li, Cheng Li, Dingbiao Mao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Vascular smooth muscle Regulator Becaplermin Down-Regulation Smad Proteins Muscle Smooth Vascular 03 medical and health sciences Downregulation and upregulation Western blot Lab/In Vitro Research Transforming Growth Factor beta Cell Movement microRNA medicine Humans RNA Messenger Cells Cultured Cell Proliferation Regulation of gene expression medicine.diagnostic_test Chemistry General Medicine Proto-Oncogene Proteins c-sis In vitro Cell biology MicroRNAs 030104 developmental biology Gene Expression Regulation Transforming growth factor Signal Transduction |
| Zdroj: | Medical Science Monitor : International Medical Journal of Experimental and Clinical Research |
| ISSN: | 1643-3750 1234-1010 |
| Popis: | BACKGROUND There is accumulating evidence demonstrating that microRNAs (miRNA) play essential roles in proliferation, migration, and invasion of vascular smooth muscle cells (VSMCs). However, the exact function of these molecules and the mechanisms involved are not fully understood. In this study, we defined the role of miR-145-5p in VSMCs. MATERIAL AND METHODS This study used the PDGF-bb-induced VSMCs proliferation model. Expression of miR-145-5p and its target, Smad4, were detected and measured by real-time PCR and Western blot analysis. The luciferase reporter of miR-145-5p was used to elucidate miRNA-target interactions. The functions of miR-145-5p in proliferation and migration were detected by CCK-8 assay, Transwell assay, and scratch test. RESULTS This study demonstrates that miR-145-5p is downregulated in PDGF-mediated VSMCs in both time- and dose-dependent manners. The in vitro results suggest that overexpression of miR-145-5p results in a reduction in SMAD4 and an increase in SMAD2, Smad3, and TGF-β at the mRNA and protein levels. Overexpression of miR-145-5p inhibited PDGF-induced VSMCs proliferation and migration. Moreover, SMAD4 was identified as a direct target of miR-145-5p and is involved in PDGF-mediated VSMC proliferation. Downstream factors such as Smad2, Smad3, and TGF-β were also influenced by miR-145-5p. CONCLUSIONS We identify miR-145-5p as a novel regulator of VSMC. Moreover, miR-145-5p inhibits VSMCs proliferation and migration by directly targeting Smad4 and dysregulating the transforming growth factor-β signaling cascade, including Smad2, Smad3, and TGF-β. |
| Databáze: | OpenAIRE |
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