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microRNA‐874 inhibition targeting STAT3 protects the heart from ischemia–reperfusion injury by attenuating cardiomyocyte apoptosis in a mouse model
Author(s) -
Chen PeiJun,
Shang AnQuan,
Yang JianPing,
Wang WeiWei
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27398
Subject(s) - stat3 , tunel assay , stat protein , apoptosis , reperfusion injury , signal transduction , biology , cardiac function curve , downregulation and upregulation , microrna , ischemia , microbiology and biotechnology , cancer research , chemistry , medicine , gene , biochemistry , heart failure
MicroRNAs (miRs) were involved in numerous cardiovascular diseases, especially ischemic heart diseases, but the miR changes during cardiac ischemia–reperfusion (I/R) injury following sevoflurane (SEV) preconditioning are still unknown. This study aims to investigate the effect of miR‐874 on cardiac I/R injury in mouse models pretreated with SEV. Following establishment of mouse models with myocardial I/R injury, mice were pretreated with SEV. The functional mechanism of miR‐874 in I/R injury was explored when miR‐874 and the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway were inhibited. Terminal deoxynucleotidyl transferase (TdT)‐mediated dUTP biotin nick‐end labeling (TUNEL) staining was used to detect cardiomyocyte apoptosis and dual luciferase reporter gene assay to identify the targeting relationship between miR‐874 and STAT3. Expression of the JAK2/STAT3 signaling pathway and apoptosis‐related genes was determined. Initially, upregulated miR‐874 was observed in I/R mice. Then, miR‐874 inhibition improved cardiac function of I/R mice, inhibited cardiomyocyte apoptosis (also shown as decreased Bcl‐2 associated X protein B [Bax] and increased B‐cell lymphoma‐2 [Bcl‐2]), and activated the JAK2/STAT3 signaling pathway. STAT3, a target gene of miR‐874, was upregulated following miR‐874 inhibition. Finally, we also observed that the effect of miR‐874 was lost when the JAK2/STAT3 signaling pathway was blocked. The findings indicate miR‐874 as a contributory role in cardiac I/R injury, with miR‐874 inhibition alleviating cardiac I/R injury in mice following SEV pretreatment by targeting STAT3 through the JAK2/STAT3 signaling pathway.