miR‑155 inhibition represents a potential valuable regulator in mitigating myocardial hypoxia/reoxygenation injury through targeting BAG5 and MAPK/JNK signaling

Abstract

increasing evidence has indicated that mir-155 is closely associated with apoptosis, which may protect the myocardium and diminish the infarct area in myocardial ischemia reperfusion injury (iri). in addition, studies have revealed that mir-155 serves a leading role in promoting fibroblast inflammation, cardiac dysfunction and other aspects of myocardial injury. The present study aimed to uncover the function and potential biological mechanism of miR-155 in myocardial iri. The rat H9c2 myocardial cells was treated with hypoxia/reoxygenation (H/r) to simulate iri in vitro. reverse transcription-quantitative polymerase chain reaction (rT-qPcr) was used to detect the expression levels of mir-155 mrna. cell counting Kit-8 and flow cytometry assays and western blot analysis were applied to determine the biological behaviors of the H/r-treated cells. The association between miR-155 and BAG family molecular chaperone regulator 5 (BAG5) was predicted by bioinformatics software and was confirmed by dual luciferase assay. RT-qPCR and western blot analysis were used to analyze the expression of BAG5. The key proteins involved in mitogen-activated protein kinase (MaPK)/JNK signaling pathway were detected by western blot analysis. The data from the rT-qPcr assay indicated that the expression of mir-155 was markedly upregulated in the H/r model, and that downregulation of mir-155 may promote cell proliferation and inhibit cell apoptosis, and vice versa. BAG5, which was downregulated in the H/R model, was confirmed as a target of miR-155 and negatively modulated by miR-155. The key proteins involved in MaPK/JnK signaling, which were highly expressed in the H/R model, were suppressed by treatment with the miR-155 inhibitor, and overexpression of BAG5 promoted the protective effect of miR-155 inhibition on cell injury caused by H/r. in addition, the expression patterns of hypoxia-inducible factor 1-α and von Hippel-lindau were altered following different treatments. Taken together, the data from the present study indicated that miR-155 inhibition represented a potential treatment strategy to improve myocardial H/R injury, which may be associated with targeting BAG5 and inhibition of the MAPK/JnK pathway.

Nano-Curcumin Protects Against Sodium Nitrite–Induced Lung Hypoxia Through Modulation of Mitogen-Activated Protein Kinases/c-Jun NH2-Terminal Kinase Signaling Pathway

“…34 Furthermore, Xi and colleagues have shown that MAPK/JNK signaling was markedly expressed in hypoxic/reoxygenated rat myocardial cell lines. 35 The results of the current study were parallel to the previous studies as the hypoxic rats exhibited significant increase in the expressions of MAPK and JNK. These observations were comparable with what was observed in a mouse model of hypoxia/reoxygenation which was triggered a typical lung injury.…”

<p>Dexmedetomidine Attenuates Cellular Injury and Apoptosis in H9c2 Cardiomyocytes by Regulating p-38MAPK and Endoplasmic Reticulum Stress</p>

“…Fortunately, numerous animal studies evaluating diverse protective mechanisms have confirmed the efficacy of cardioprotection in ameliorating MIRI. [1][2][3][4][5][6] The actual clinical application of some of these strategies, however, does not match the animal study applications, and it is difficult to predict the consequences in clinical practice from those seen in experimental research. [7][8][9] In this context, the unclear mechanism underlying the development of apoptotic pathways or involving key molecules in MIRI might significantly matter, especially for cell death and even associated signalling pathways during ischaemia-reperfusion, such as ERS-related apoptosis or signalling pathways; a noteworthy report by Davidson in 2019 shared the opinion that multitarget strategies must be adopted to reduce MIRI if appropriate because single approaches have a limited capacity to overcome complicated MIRI situations.…”

Adipose tissue macrophages as a therapeutic target in obesity‐associated diseases

“…Another remarkable study showed recently that ATMs from obese mice secrete exosomal miRNAs, and when these ATMs are administrated to lean mice, they induce glucose intolerance and IR, observations that may explain, in part, how miR‐155 exerts its effects on cellular insulin signaling 128 . Interestingly, a recent study has shown that miR‐155 stimulates JNK activity in myocardial cells, thereby promoting cell injury in an hypoxia/reoxygenation model in vitro 129 . Thus, there is the intriguing possibility that exosomal miR‐155 production by ATMs could promote JNK activity in an autocrine manner, thus increasing M1‐polarization in ATMs and inducing IR.…”

“…128 Interestingly, a recent study has shown that miR-155 stimulates JNK activity in myocardial cells, thereby promoting cell injury in an hypoxia/reoxygenation model in vitro. 129 Thus, there is the intriguing possibility that exosomal miR-155 production by ATMs could promote JNK activity in an autocrine manner, thus increasing M1-polarization in ATMs and inducing IR. More studies are necessary to test this idea.…”