PMID- 34795497
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220428
IS  - 1178-7031 (Print)
IS  - 1178-7031 (Electronic)
IS  - 1178-7031 (Linking)
VI  - 14
DP  - 2021
TI  - circ_TGFBR2 Inhibits Vascular Smooth Muscle Cells Phenotypic Switch and 
      Suppresses Aortic Dissection Progression by Sponging miR-29a.
PG  - 5877-5890
LID - 10.2147/JIR.S336094 [doi]
AB  - BACKGROUND: Aortic dissection (AD) is a threatening and catastrophic vascular 
      disease with high mortality rate and limited therapeutic strategies. There is 
      emerging evidence showing that circular RNAs play crucial role in regulating 
      various cardiovascular diseases. However, the biological functions and molecular 
      mechanisms of circRNAs in AD still remains elusive. The purpose of this study was 
      to illustrate the potential functional roles and mechanisms of hsa_circ_TGFBR2 in 
      vitro and in vivo. METHODS: The vascular smooth muscle cells (VSMCs) and AD-VSMCs 
      were isolated from normal aorta and AD tissues. The expression of circ_TGFBR2, 
      miR-29a and KLF4 were detected by realtime polymerase chain reaction (RT-PCR) and 
      fluorescence in situ hybridization (FISH). Cell proliferation was assessed by 
      CCK-8 assay, colony formation and EDU assay. Cell migration was evaluated through 
      transwell assay. Dual-luciferase reporter assay and RNA pulldown were performed 
      to identify the interaction between circ_TGFBR2 and miR-29a or between miR-29a 
      and KLF4. The wild-type sequence of circ_TGFBR2 or KLF4 were cloned into the 
      luciferase reporter plasmid, and the activity was measured using dual-luciferase 
      reporter assay system. And for RNA pulldown, the relative RNA enrichment of 
      circ_TGFBR2 and miR-29a were confirmed using RT-PCR. Western Blot measured the 
      expression of phenotype switch-related proteins. AD rat model induced by 
      beta-aminopropionitrile monofumarate (BAPN) was used to verify the role and 
      mechanism of circ_TGFBR2. RESULTS: Circ_TGFBR2 inhibited cell proliferation and 
      migration of AD-VSMCs cells. Overexpression of circ_TGFBR2 promoted the 
      expression of contractile markers (alpha-SMA, SM22alpha) and inhibited the expression of 
      synthetic markers (MGP, OPN) in AD-VSMCs cells. Circ_TGFBR2 served as a sponge 
      for miR-29a targeting KLF4. MiR-29a mimics rescued biological roles induced by 
      circ_TGFBR2 overexpression. The in vivo experiments revealed that overexpression 
      of TGFBR2 suppressed the progression of AD and increased the expression of 
      contractile markers while inhibited the expression of synthetic markers. 
      CONCLUSION: Our study revealed that circ_TGFBR2 regulated VSMCs phenotype switch 
      and suppressed the progression of AD.
CI  - (c) 2021 Xu et al.
FAU - Xu, Zhenjun
AU  - Xu Z
AD  - Department of Thoracic and Cardiovascular Surgery, Nanjing Drum Tower Hospital, 
      The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, 
      People's Republic of China.
FAU - Zhong, Kai
AU  - Zhong K
AD  - Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, 
      Nanjing, 210008, People's Republic of China.
FAU - Guo, Guanjun
AU  - Guo G
AD  - Department of Thoracic and Cardiovascular Surgery, Nanjing Drum Tower Hospital, 
      The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, 
      People's Republic of China.
FAU - Xu, Can
AU  - Xu C
AD  - Department of Thoracic and Cardiovascular Surgery, Nanjing Drum Tower Hospital, 
      The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, 
      People's Republic of China.
FAU - Song, Zhizhao
AU  - Song Z
AD  - Department of Thoracic and Cardiovascular Surgery, Nanjing Drum Tower Hospital, 
      The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, 
      People's Republic of China.
FAU - Wang, Dongjin
AU  - Wang D
AD  - Department of Thoracic and Cardiovascular Surgery, Nanjing Drum Tower Hospital, 
      The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, 
      People's Republic of China.
FAU - Pan, Jun
AU  - Pan J
AD  - Department of Thoracic and Cardiovascular Surgery, Nanjing Drum Tower Hospital, 
      The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, 
      People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20211109
PL  - New Zealand
TA  - J Inflamm Res
JT  - Journal of inflammation research
JID - 101512684
PMC - PMC8593842
OTO - NOTNLM
OT  - KLF4
OT  - aortic dissection
OT  - circ_TGFBR2
OT  - miR-29a
OT  - vascular smooth muscle cells
COIS- There is no conflict of interest to declare in this research.
EDAT- 2021/11/20 06:00
MHDA- 2021/11/20 06:01
PMCR- 2021/11/09
CRDT- 2021/11/19 06:52
PHST- 2021/08/30 00:00 [received]
PHST- 2021/10/22 00:00 [accepted]
PHST- 2021/11/19 06:52 [entrez]
PHST- 2021/11/20 06:00 [pubmed]
PHST- 2021/11/20 06:01 [medline]
PHST- 2021/11/09 00:00 [pmc-release]
AID - 336094 [pii]
AID - 10.2147/JIR.S336094 [doi]
PST - epublish
SO  - J Inflamm Res. 2021 Nov 9;14:5877-5890. doi: 10.2147/JIR.S336094. eCollection 
      2021.