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.

<p>Dexmedetomidine protects H9c2 cardiomyocytes against oxygen-glucose deprivation/reoxygenation-induced intracellular calcium overload and apoptosis through regulating FKBP12.6/RyR2 signaling</p>

“…1,2 Studies identified various molecular and cellular mechanisms involved in the process of myocardial I/R. [3][4][5][6][7] Of these, intracellular calcium [Ca 2+ ]i overload is a critical one that leads to cardiomyocyte apoptosis and cell death. [8][9][10] Dexmedetomidine (DEX) is a highly selective α2-adrenoceptor agonist with sedative, anxiolytic, analgesic, and sympatholytic properties.…”

The potential function ofmiR‐135b‐mediated JAK2/STAT3 signaling pathway during osteoblast differentiation

“…Xie et al also verified that miR-135b inhibition caused an increase in the expression of JAK2, resulting in the activation of JAK2/STAT3 and protecting the myocardial cells from the ischemia-reperfusion injury. 35 Increasing evidence has shown that JAK2 activation would give rise to the interactive phosphorylation of the residues of tyrosine, and the resultant p-JAK2 provided the anchor sites for the downstream STAT3. Under the phosphorylation, STAT3 would be activated and transferred into the nucleus to regulate the gene transcription and protein expression; here, JAK2/STAT3 signaling pathway was fully activated.…”

Apigenin Alleviates Myocardial Reperfusion Injury in Rats by Downregulating miR-15b

“…miRNA induces cleavage or blockage of translation of the target mRNAs by complete or incomplete complementary binding to the 3′ untranslated region (UTR) of mRNAs. The role of abnormal expression and function in myocardial [12], spinal cord [13], and renal [14] I-R injury has attracted increasing attention. Studies have shown that miR-15b plays a role in the I-R injury of cardiomyocytes [15,16] and nerve cells [17].…”

“…Studies have shown that apigenin is closely related to JAK2-STAT3 pathway activity and ischemia-reperfusion injury [22]. The activity of the JAK2-STAT3 pathway is closely related to injury to the heart [8,10,12], kidneys [7,9], and brain [11]. Luo found that osthole reduced renal reperfusion injury by regulating JAK2-STAT3 pathway activity [7].…”