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

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. C57BL/6 mice were used to produce a model of arterial injury in vivo. Mouse arterial SMCs were isolated for in vitro 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. 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. The overexpression of RUNX2 elevated the expression of miR-23, thus inhibiting TGFBR2 and promoting vascular injury repair. 2021 Annals of Translational Medicine. All rights reserved.

Citation

Kai Wu, Zhou Cai, Bo Liu, Yu Hu, Pu Yang. RUNX2 promotes vascular injury repair by activating miR-23a and inhibiting TGFBR2. Annals of translational medicine. 2021 Mar;9(5):363

PMID: 33842584

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