A microRNA-17-5p/homeobox B13 axis participates in the phenotypic modulation of vascular smooth muscle cells
| Autor: | Guoping Zhao, Hui Zhang, Kun Zhou, Tianchi Yu, Shifang Kuang, Tao Wang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Cancer Research Vascular smooth muscle proliferation Myocytes Smooth Muscle Becaplermin Down-Regulation Muscle Proteins Biology migration Biochemistry Muscle Smooth Vascular Sincalide Rats Sprague-Dawley Cell Movement Proliferating Cell Nuclear Antigen microRNA Gene expression Genetics vascular smooth muscle cells Animals Molecular Biology Cell Proliferation Homeodomain Proteins Gene knockdown Cell growth Microfilament Proteins phenotypic switching Cell migration Articles Cell cycle microRNA-17-5p homeobox B13 Cell biology Rats MicroRNAs Oncology Gene Expression Regulation Matrix Metalloproteinase 9 Gene Knockdown Techniques Molecular Medicine Smoothelin Matrix Metalloproteinase 2 |
| Zdroj: | Molecular Medicine Reports |
| ISSN: | 1791-3004 1791-2997 |
| Popis: | Vascular smooth muscle cells (VSMCs) serve a decisive role in intimal hyperplasia, a common pathophysiological process that leads to numerous vascular disorders. The present study aimed to investigate the unknown mechanisms underlying VSMC phenotypic modulation and identified a novel microRNA (miRNA/miR)‑17‑5p/homeobox B13 (HOXB13) axis involved in the phenotypic switching, proliferation and migration of VSMCs. VSMCs were isolated from the thoracic aorta of Sprague‑Dawley rats, cell proliferation was determined by Cell Counting Kit‑8 (CCK‑8) assay, cell migration was examined by Transwell migration assay and gene expression was detected using reverse transcription‑quantitative PCR and western blot analyses. It was firstly found that incubation with platelet‑derived growth factor‑BB (PDGF‑BB) recombinant protein resulted in a significant increase in HOXB13 expression in VSMCs. Using multiple miRNA prediction tools, miR‑17‑5p was identified as a potential regulator for HOXB13, since it had a 7‑base perfect binding site and a 5‑base imperfect binding site with the 3'‑untranslated region of HOXB13 mRNA, and these sequences were highly conserved across species. The regulatory effect of miR‑17‑5p on HOXB13 was validated using luciferase reporter assays. The expression level of miR‑17‑5p was increased in VSMCs under PDGF‑BB stimulation, and was negatively correlated with HOXB13 mRNA and protein expression. Moreover, the miR‑17‑5p mimics significantly inhibited the proliferation and migration of VSMCs, while antagomiR‑17‑5p showed the opposite effects, which could be abolished by HOXB13 knockdown. The miR‑17‑5p/HOXB13 axis also regulated the expression levels of the markers of differentiated VSMCs (α‑smooth muscle actin, transgelin and smoothelin), proliferating cell nuclear antigen and cell migration proteins, including MMP‑2 and ‑9. In conclusion, the present study demonstrated that miR‑17‑5p inhibited the phenotypic modulation VSMCs stimulated by PDGF‑BB by downregulating HOXB13, indicating that these factors may be potential therapeutic targets for intimal hyperplasia. |
| Databáze: | OpenAIRE |
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