MicroRNA‐494 regulates high glucose‐induced cardiomyocyte apoptosis and autophagy by PI3K/AKT/mTOR signalling pathway

Abstract

Aims Diabetic cardiomyopathy (DCM) is one of the major cardiovascular complications of diabetes. However, the mechanism of DCM is not fully understood. Studies have confirmed that certain microRNAs (miRNAs/miRs) are key regulators of DCM. The aim of this study was to investigate the role and mechanism of microRNA (miR)‐494 in cardiomyocyte apoptosis and autophagy induced by high glucose (HG). Methods and results By establishing a rat DCM model and an HG‐treated H9c2 cells injury model, cardiac function was detected by echocardiography, myocardial tissue was stained by immunohistochemistry, and Cell Counting Kit‐8 assay and lactate dehydrogenase assay were used to detect the cardiomyocyte injury. Cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labelling staining, and western blotting was used to detect death and autophagy. The results showed that the expression level of miR‐494 was higher in the myocardial tissue of DCM rats and the myocardial cells of H9c2 treated with HG. Compared with the corresponding negative control groups, miR‐494 mimics enhanced HG‐induced apoptosis and autophagy, whereas miR‐494 inhibitors showed the opposite effect, corresponding PI3K, AKT, and mTOR phosphorylation level has changed. Conclusions These findings identify that miR‐494 could regulate cell apoptosis and autophagy through PI3K/AKT/mTOR signalling pathway, participating in the regulation of cardiomyocyte cell damage after HG. These findings provide new insights for the further study of the molecular mechanism and treatment of DCM.

Pec 1 of Pseudomonas aeruginosa Inhibits Bacterial Clearance of Host by Blocking Autophagy in Macrophages

“…Accumulating studies have demonstrated miRNAs directly target PI3K or its downstream components, which critically contributes to extensive cell events, including autophagy. , A previous study revealed that miR-155 mediated autophagy via directly targeting PI3K-AKT-mTOR in Schwann cells . We hypothesized that PI3K was also targeted by miR-155 to regulate Pec 1-induced autophagy inhibition in MH-S cells.…”

Exploring the mechanism of diabetic cardiomyopathy treated with Qigui Qiangxin mixture based on UPLC-Q/TOF-MS, network pharmacology and experimental validation

“…The PI3K-Akt signaling pathway can regulate various cellular processes, which are closely related to cell proliferation, growth, metastasis, and apoptosis [33] . The PI3K-Akt signaling pathway has been found to play a cardioprotective role in cardiomyocytes by inhibiting apoptosis [34,35] . PI3K, fully known as phosphatidylinositol 3-kinase, has three different types [36] , of which only class I can act as lipid phosphorylator upon upstream signaling stimulation [37] .…”

Exploring the mechanism of diabetic cardiomyopathy treated with Qigui Qiangxin mixture based on UPLC-Q/TOF-MS, network pharmacology and experimental validation

“…The PI3K-Akt signaling pathway can regulate various cellular processes, which are closely related to cell proliferation, growth, metastasis, and apoptosis 33 . The PI3K-Akt signaling pathway has been found to play a cardioprotective role in cardiomyocytes by inhibiting apoptosis 34 , 35 . PI3K, fully known as phosphatidylinositol 3-kinase, has three different types 36 , of which only class I can act as lipid phosphorylator upon upstream signaling stimulation 37 .…”