miR-155-5p upregulation ameliorates myocardial insulin resistance via mTOR signaling in chronic alcohol drinking rats

Abstract

Background Chronic alcohol intake is associated with an increased risk of alcoholic cardiomyopathy, which may present with pathological changes such as myocardial insulin resistance, leading to ventricular dilation and cardiac dysfunction. Although a correlation between microRNA-155 (miR-155) and insulin signaling has been identified, the underlying mechanism has not been elucidated to date. The purpose of the study was to determine whether overexpression of miR-155-5p in vivo could ameliorate chronic alcohol-induced myocardial insulin resistance and cardiac dysfunction. Material and Methods Wistar rats were fed with either alcohol or water for 20 weeks to establish chronic alcohol intakes model. Then the alcohol group were divided into three groups: model group, miRNA-155 group and AAV-NC group. Rats undergoing alcohol treatment were injected with AAV-miRNA-155 (adeno-associated virus 9) or its negative control AAV-NC, respectively. Gene expression was determined by real-time PCR, and protein expression was determined by western blot. Echocardiography was performed to assess terminal cardiac function. Insulin responsiveness was determined through the quantification of phosphorylated insulin receptor substrate 1 (ser 307) and phosphorylated insulin receptor (Tyr 1185) levels. Results We found that cardiac function was attenuated in chronic alcohol intake rats, with an activated mammalian target of rapamycin (mTOR) signaling pathway, accompanied by an increase in p-IRS1(ser 307) and a decrease in p-IR (Tyr 1185) level in myocardial tissue. Also, alcohol drinking significantly up-regulated miR-155-5p level and its overexpression decreased p-IRS1 (ser 307) and increased p-IR (Tyr 1185) levels, and meanwhile inhibited the mTOR signaling pathway. Conclusion miR-155-5p upregulation ameliorates myocardial insulin resistance via the mTOR signaling in chronic alcohol drinking rats. We propose that miR-155 may serve as a novel potential therapeutic target for alcoholic heart disease.

MiR-23b-3p Improves Brain Damage after Status Epilepticus by Reducing the Formation of Pathological High-Frequency Oscillations via Inhibition of cx43 in Rat Hippocampus

“…Both autophagy and miRNAs are involved in synaptic remodeling, neuronal plasticity, proliferation, apoptosis, and inflammation. ,, We speculate that a miRNA-autophagy pathway could play a role in the occurrence of epilepsy. For example, miRNA-155 has been reported to induce autophagy via the mTOR pathway . Beclin 1 is mainly located in cytoplasm in both human and rat cells; thus, miRNA could be involved in the regulation of Beclin 1 .…”

“…For example, miRNA-155 has been reported to induce autophagy via the mTOR pathway. 28 Beclin 1 is mainly located in cytoplasm in both human and rat cells; thus, miRNA could be involved in the regulation of Beclin 1. 29 Beclin1 is an evolutionarily conserved protein that is recognized as a positive regulatory factor in the biogenesis of autophagosomes.…”

Circulating microRNAs as potential biomarkers of early vascular damage in vitamin D deficiency, obese, and diabetic patients

“…Changes in miR-155-5p were reported in several studies in both animal and human models related to diabetes mellitus and cardiovascular pathogeneses. A recent study has reported that miR-155-5p upregulation affects myocardial insulin resistance via mTOR signaling in chronic alcohol-drinking rats [ 48 ]. Additionally, miR-155 deletion in female mice increases adipogenic, insulin sensitivity, and energy uncoupling machinery, while limiting inflammation in white adipose tissue, which together could restrict high-fat diet-induced fat accumulation.…”

Acteoside attenuates hydrogen peroxide-induced injury of retinal ganglion cells via the CASC2/miR-155/mTOR axis

“…Notably, the expression of miR-155 is upregulated in the (31). Several studies show that the mTOR signaling pathway is involved in miR-155-mediated regulation (16,22). In addition, mTOR contributes to glaucoma development and is associated with RGC activity (13,32,33).…”

“…Given that miR-155 functions via mTOR signaling (22) and mTOR was involved in RGC damage and glaucoma development (8), we next determined the role of mTOR in the protective effect of acteoside/miR-155 on RGC-5 cells. It was found that mTOR expression was decreased in H 2 O 2treated RGC-5 cells (Figure 6A), and miR-155 inhibition could induce mTOR expression (Figure 6B).…”