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Cited by 7MicroRNA in disease regulationTGF-β signaling in diseasesRenin-Angiotensin System Studies

RUNX2 promotes vascular injury repair by activating miR-23a and inhibiting TGFBR2

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Wu, Kai, Cai, Zhou, Liu, Bo, Hu, Yu, Yang, Pu·2021·Annals of Translational Medicine
DOI 10.21037/atm-20-2661PMC PMC8033336
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Abstract

BACKGROUND: Previous evidence has suggested that the transcription factor, runt-related transcription factor 2 (RUNX2), promotes the repair of vascular injury and activates the expression of microRNA-23a (miR-23a). TGF-β receptor type II (TGFBR2) has been found to mediate smooth muscle cells (SMCs) following arterial injury. However, the interactions among RUNX2, miR-23a and TGFBR2 in vascular injury have not been investigated thoroughly yet. Therefore, we aim to explore the mechanism of how RUNX2 triggers the expression of miR-23a and its effects on the repair of vascular injury. METHODS: cell injury induction by 100 nmol/L tumor necrosis factor-α (TNF-α). Gain-and loss-of-function studies were conducted to assess cell viability and apoptosis by using cell counting kit (CCK)-8 assay and flow cytometry respectively. The levels of TNF-α, interleukin-6 (IL-6), and monocyte chemotactic protein-1 (MCP-1) were examined by enzyme-linked immunosorbent assay (ELISA). The interaction between RUNX2 and miR-23a was identified by chromatin immunoprecipitation (ChIP) and dual luciferase reporter assays, while the targeting relationship between miR-23a and TGFBR2 was analyzed by RNA immunoprecipitation (RIP) and dual luciferase reporter assays. RESULTS: Both RUNX2 and miR-23a exhibited low levels of expressions, while TGFBR2 had a high level of expression in mice with induced arterial injury. RUNX2 was found to bind to the promoter of miR-23a and activate miR-23a, while miR-23a targeted TGFBR2. Ectopic RUNX2 expression inhibited inflammatory cell infiltration, and promoted collagen content by upregulating miR-23a and downregulating TGFBR2. Furthermore, the overexpression of RUNX2 increased viability and decreased apoptosis in vascular smooth muscle cells (VSMCs) by activating miR-23a. CONCLUSIONS: The overexpression of RUNX2 elevated the expression of miR-23, thus inhibiting TGFBR2 and promoting vascular injury repair.

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  • As a target gene of miR-23a, TGFR2 is subsequently downregulated, leading to an increase in the vitality of vascular smooth muscle cells and a reduction in cell apoptosis.

    “As a target gene of miR-23a, TGF receptor type 2 (TGFR2) is subsequently downregulated, leading to an increase in the vitality of vascular smooth muscle cells (VSMCs) and a reduction in cell apoptosis [48].”

    From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [48]

  • In an arterial injury model of 57 BL/6 mice, miR-23a can be regulated by RUNX2 binding to the promoter of miR-23a to activate its expression.

    “It is worth noting that in the vascular injury repair study conducted on the arterial injury model of 57 BL/6 mice, miR-23a can be regulated by other transcription factors, such as RUNX2 binding to the promoter of miR-23a to activate its expression.”

    From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [48]

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Authors
Wu, K., Cai, Z., Liu, B., Hu, Y., & Yang, P.
Affiliations
Central South University (CN)
Corresponding author
Yang, Pu
ORCID
Venue
Annals of Translational Medicine
Publisher
AME Publishing Company
Published
2021-03
Volume
9
Issue
5
Pages
363-363
ISSN
  • 2305-5839 (ISSN-L)
  • 2305-5847
DOI
10.21037/atm-20-2661
PMC
PMC8033336
OpenAlex
W3138098911
Cited by
7
References
35
Citations by year
2026: 1 · 2024: 3 · 2023: 1 · 2021: 2
FWCI
0.60
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Annals of Translational Medicine (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China
  • Natural Science Foundation of Hunan Province
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
Keywords
Runx2, miR-23a, TGFBR2, vascular injury repair, arterial injury, vascular smooth muscle cells, microRNA regulation, TGF-beta signaling, inflammation, collagen deposition, apoptosis, TNF-α

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