Suppression of microRNA-135b-5p protects against myocardial ischemia/reperfusion injury by activating JAK2/STAT3 signaling pathway in mice during sevoflurane anesthesia.

Abstract

The study aims to explore the effects of miR-135b-5p on myocardial ischemia/reperfusion (I/R) injuries by regulating Janus protein tyrosine kinase 2 (JAK2)/signal transducer and activator of transcription (STAT) signaling pathway by mediating inhalation anesthesia with sevoflurane. A sum of 120 healthy Wistar male mice was assigned into six groups. Left ventricular ejection fraction (LVEF) and left ventricular shortening fraction (LVSF) were detected. Cardiomyocyte apoptosis was determined by terminal dexynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) assay. MiR-135b-5p expression, mRNA and protein expression of p-STAT3, p-JAK2, STAT3, JAK2, B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein B (Bax) were detected by quantitative real-time PCR (qRT-PCR) and Western blotting. Target relationship between miR-135b-5p and JAK2 was confirmed by dual-luciferase reporter assay. The other five groups exhibited increased cardiomyocyte necrosis, apoptosis, miR-135b-5p and Bax expression, mRNA expression of JAK2 and STAT3, and protein expression of p-STAT3 and p-JAK2 compared with the sham group, but showed decreased LVEF, LVFS, and Bcl-2 expression. Compared with the model and AG490 + Sevo groups, the Sevo, inhibitor + Sevo and inhibitor + AG490 + Sevo groups displayed reduced cardiomyocyte necrosis, apoptosis, miR-135b-5p and Bax expression, but displayed elevated mRNA expression of JAK2 and STAT3, protein expression of p-STAT3 and p-JAK2, LVEF, LVFS and Bcl-2 expression. Compared with the Sevo and inhibitor + AG490 + Sevo groups, the AG490 + Sevo group showed decreased LVEF, LVFS, Bcl-2 expression, mRNA expressions of JAK2 and STAT3, and protein expressions of p-STAT3 and p-JAK2, but increased cardiomyocyte necrosis, apoptosis, and Bax expressions. MiR-135b-5p negatively targetted JAK2. Inhibition of miR-135b-5p can protect against myocardial I/R injury by activating JAK2/STAT3 signaling pathway through mediation of inhalation anesthesia with sevoflurane.

• Authors: Xiao-Juan Xie, Dong-Mei Fan, Kai Xi, Ya-Wei Chen, Peng-Wei Qi, Qian-Hui Li, Liang Fang, Li-Gang Ma
• Journal: Bioscience reports (Biosci Rep) Vol. 37 Issue 3 (Jun 30 2017) ISSN: 1573-4935 [Electronic] England
• PMID: 28522550 (Publication Type: Journal Article, Retracted Publication)
• Copyright: © 2017 The Author(s).

Chemical References

• Anesthetics, Inhalation
• Methyl Ethers
• MicroRNAs
• Mirn135 microRNA, mouse
• STAT3 Transcription Factor
• Sevoflurane
• Janus Kinase 2

Topics

• Anesthetics, Inhalation (therapeutic use)
• Animals
• Apoptosis (drug effects)
• Down-Regulation (drug effects)
• Gene Expression Regulation (drug effects)
• Janus Kinase 2 (genetics, metabolism)
• Male
• Methyl Ethers (therapeutic use)
• Mice
• MicroRNAs (antagonists & inhibitors, genetics)
• Myocardial Reperfusion Injury (genetics, metabolism, pathology, therapy)
• Myocardium (metabolism, pathology)
• Myocytes, Cardiac (drug effects, metabolism, pathology)
• STAT3 Transcription Factor (genetics, metabolism)
• Sevoflurane
• Signal Transduction (drug effects)