PMID- 33842584
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220422
IS  - 2305-5839 (Print)
IS  - 2305-5847 (Electronic)
IS  - 2305-5839 (Linking)
VI  - 9
IP  - 5
DP  - 2021 Mar
TI  - RUNX2 promotes vascular injury repair by activating miR-23a and inhibiting 
      TGFBR2.
PG  - 363
LID - 10.21037/atm-20-2661 [doi]
LID - 363
AB  - 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-beta 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: 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-alpha (TNF-alpha). 
      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-alpha, 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.
CI  - 2021 Annals of Translational Medicine. All rights reserved.
FAU - Wu, Kai
AU  - Wu K
AD  - Department of Rehabilitation, Xiangya Hospital, Central South University, 
      Changsha, China.
FAU - Cai, Zhou
AU  - Cai Z
AD  - Department of General & Vascular Surgery, Xiangya Hospital, Central South 
      University, Changsha, China.
FAU - Liu, Bo
AU  - Liu B
AD  - Department of General Surgery, The Second Xiangya Hospital, Central South 
      University, Changsha, China.
FAU - Hu, Yu
AU  - Hu Y
AD  - Center for Experimental Medical Research, The Third Xiangya Hospital, Central 
      South University, Changsha, China.
FAU - Yang, Pu
AU  - Yang P
AD  - Department of General & Vascular Surgery, Xiangya Hospital, Central South 
      University, Changsha, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Ann Transl Med
JT  - Annals of translational medicine
JID - 101617978
PMC - PMC8033336
OTO - NOTNLM
OT  - Runt-related transcription factor 2 (RUNX2)
OT  - TGF-beta receptor type II (TGFBR2)
OT  - artery injury
OT  - microRNA-23a (miR-23a)
OT  - vascular injury repair
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at http://dx.doi.org/10.21037/atm-20-2661). The authors have no 
      conflicts of interest to declare.
EDAT- 2021/04/13 06:00
MHDA- 2021/04/13 06:01
PMCR- 2021/03/01
CRDT- 2021/04/12 06:25
PHST- 2021/04/12 06:25 [entrez]
PHST- 2021/04/13 06:00 [pubmed]
PHST- 2021/04/13 06:01 [medline]
PHST- 2021/03/01 00:00 [pmc-release]
AID - atm-09-05-363 [pii]
AID - 10.21037/atm-20-2661 [doi]
PST - ppublish
SO  - Ann Transl Med. 2021 Mar;9(5):363. doi: 10.21037/atm-20-2661.