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A microRNA‑17‑5p/homeobox B13 axis participates in the phenotypic modulation of vascular smooth muscle cells

  • Authors:
    • Tianchi Yu
    • Tao Wang
    • Shifang Kuang
    • Guoping Zhao
    • Kun Zhou
    • Hui Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Vascular Surgery, Jiangning Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 211100, P.R. China, Center of Endoscopy, Jiangning Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 211100, P.R. China, Department of General Surgery, Jiangning Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 211100, P.R. China
    Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 731
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    Published online on: August 16, 2021
       https://doi.org/10.3892/mmr.2021.12370
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Abstract

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.
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Copy and paste a formatted citation
Spandidos Publications style
Yu T, Wang T, Kuang S, Zhao G, Zhou K and Zhang H: A microRNA‑17‑5p/homeobox B13 axis participates in the phenotypic modulation of vascular smooth muscle cells. Mol Med Rep 24: 731, 2021.
APA
Yu, T., Wang, T., Kuang, S., Zhao, G., Zhou, K., & Zhang, H. (2021). A microRNA‑17‑5p/homeobox B13 axis participates in the phenotypic modulation of vascular smooth muscle cells. Molecular Medicine Reports, 24, 731. https://doi.org/10.3892/mmr.2021.12370
MLA
Yu, T., Wang, T., Kuang, S., Zhao, G., Zhou, K., Zhang, H."A microRNA‑17‑5p/homeobox B13 axis participates in the phenotypic modulation of vascular smooth muscle cells". Molecular Medicine Reports 24.4 (2021): 731.
Chicago
Yu, T., Wang, T., Kuang, S., Zhao, G., Zhou, K., Zhang, H."A microRNA‑17‑5p/homeobox B13 axis participates in the phenotypic modulation of vascular smooth muscle cells". Molecular Medicine Reports 24, no. 4 (2021): 731. https://doi.org/10.3892/mmr.2021.12370
Copy and paste a formatted citation
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Spandidos Publications style
Yu T, Wang T, Kuang S, Zhao G, Zhou K and Zhang H: A microRNA‑17‑5p/homeobox B13 axis participates in the phenotypic modulation of vascular smooth muscle cells. Mol Med Rep 24: 731, 2021.
APA
Yu, T., Wang, T., Kuang, S., Zhao, G., Zhou, K., & Zhang, H. (2021). A microRNA‑17‑5p/homeobox B13 axis participates in the phenotypic modulation of vascular smooth muscle cells. Molecular Medicine Reports, 24, 731. https://doi.org/10.3892/mmr.2021.12370
MLA
Yu, T., Wang, T., Kuang, S., Zhao, G., Zhou, K., Zhang, H."A microRNA‑17‑5p/homeobox B13 axis participates in the phenotypic modulation of vascular smooth muscle cells". Molecular Medicine Reports 24.4 (2021): 731.
Chicago
Yu, T., Wang, T., Kuang, S., Zhao, G., Zhou, K., Zhang, H."A microRNA‑17‑5p/homeobox B13 axis participates in the phenotypic modulation of vascular smooth muscle cells". Molecular Medicine Reports 24, no. 4 (2021): 731. https://doi.org/10.3892/mmr.2021.12370
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