PMID- 31997826
OWN - NLM
STAT- MEDLINE
DCOM- 20201124
LR  - 20210203
IS  - 1643-3750 (Electronic)
IS  - 1234-1010 (Print)
IS  - 1234-1010 (Linking)
VI  - 26
DP  - 2020 Jan 30
TI  - MicroRNA-668-3p Protects Against Oxygen-Glucose Deprivation in a Rat H9c2 
      Cardiomyocyte Model of Ischemia-Reperfusion Injury by Targeting the Stromal 
      Cell-Derived Factor-1 (SDF-1)/CXCR4 Signaling Pathway.
PG  - e919601
LID - 10.12659/MSM.919601 [doi]
AB  - BACKGROUND Ischemia-reperfusion injury (IRI) results from the restoration of 
      blood supply to ischemic organs, including the heart. Expression of 
      microRNA-668-3p (miR-668-3p) is known to protect the kidney from IRI. This study 
      aimed to investigate the role of miR-668-3p in oxygen-glucose deprivation (OGD) 
      in a rat H9c2 cardiomyocyte model of IRI. MATERIAL AND METHODS Rat H9c2 
      cardiomyocytes were cultured in glucose-free Dulbecco's modified Eagle's medium 
      (DMEM) under anaerobic conditions, followed by oxygenation, to create the OGD 
      model of IRI. The luciferase reporter assay evaluated the interaction between 
      stromal cell-derived factor-1 (SDF-1), or CXC motif chemokine 12 (CXCL12), and 
      miR-668-3p. Protein and mRNA levels of SDF-1, CXCR4, Bcl2, Bax, cleaved 
      caspase-3, endothelial nitric oxide synthase (eNOS), and phosphorylated 
      endothelial nitric oxide synthase (p-eNOS) were analyzed by Western blot and 
      quantitative reverse transcription-polymerase chain reaction (RT-qPCR), and 
      apoptosis were assessed by flow cytometry. Enzyme-linked immunosorbent assay 
      (ELISA) measured reactive oxygen species (ROS), including malondialdehyde (MDA), 
      nitric oxide (NO), p-eNOS, and the inflammatory cytokines, tumor necrosis 
      factor-alpha (TNF-alpha), interleukin-1ss (IL-1ss), IL-6, and monocyte 
      chemoattractant protein-1 (MCP-1) in H9c2 cell supernatants. RESULTS In the OGD 
      rat H9c2 cardiomyocyte model of IRI, miR-668-3p levels were reduced. 
      Overexpression of miR-668-3p inhibited SDF-1, CXCR4, the expression of 
      inflammatory cytokines, markers of oxidative stress, and p-eNOS. The 
      overexpression of SDF-1 reversed these findings. Overexpression of SDF-1 promoted 
      cell apoptosis, which was reduced by miR-668-3p. CONCLUSIONS In the OGD rat H9c2 
      cardiomyocyte model of IRI, miR-668-3p suppressed mediators of inflammation and 
      oxidative stress and enhanced cell viability through the SDF-1/CXCR4 signaling 
      pathway.
FAU - Gao, Zhan
AU  - Gao Z
AD  - Department of Cardiovascular Surgery, Children's Hospital of Zhejiang University, 
      School of Medicine, Hangzhou, Zhejiang, China (mainland).
FAU - Gao, Qiang
AU  - Gao Q
AD  - Department of Cardiovascular Surgery, Children's Hospital of Zhejiang University, 
      School of Medicine, Hangzhou, Zhejiang, China (mainland).
FAU - Lv, Xiaodong
AU  - Lv X
AD  - Department of Cardiovascular Surgery, Fuwai Hospital, Chinese Academy of Medical 
      Sciences and Peking Union Medical College, Beijing, China (mainland).
LA  - eng
PT  - Journal Article
DEP - 20200130
PL  - United States
TA  - Med Sci Monit
JT  - Medical science monitor : international medical journal of experimental and 
      clinical research
JID - 9609063
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Cxcr4 protein, rat)
RN  - 0 (MIRN668 microRNA, rat)
RN  - 0 (MicroRNAs)
RN  - 0 (Receptors, CXCR4)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - IY9XDZ35W2 (Glucose)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Apoptosis/genetics
MH  - Base Sequence
MH  - Cell Line
MH  - Chemokine CXCL12/*metabolism
MH  - Glucose/*deficiency
MH  - MicroRNAs/genetics/*metabolism
MH  - *Models, Biological
MH  - Myocytes, Cardiac/*metabolism/pathology
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase Type III/metabolism
MH  - Oxidative Stress/genetics
MH  - Oxygen/*metabolism
MH  - Rats
MH  - Receptors, CXCR4/*metabolism
MH  - Reperfusion Injury/*genetics/pathology
MH  - Signal Transduction
PMC - PMC7003666
COIS- Conflicts of interest None.
EDAT- 2020/01/31 06:00
MHDA- 2020/11/25 06:00
PMCR- 2020/01/30
CRDT- 2020/01/31 06:00
PHST- 2020/01/31 06:00 [entrez]
PHST- 2020/01/31 06:00 [pubmed]
PHST- 2020/11/25 06:00 [medline]
PHST- 2020/01/30 00:00 [pmc-release]
AID - 919601 [pii]
AID - 10.12659/MSM.919601 [doi]
PST - epublish
SO  - Med Sci Monit. 2020 Jan 30;26:e919601. doi: 10.12659/MSM.919601.