GAS5 regulates diabetic cardiomyopathy via miR-221-3p/p27 axis-associated autophagy

Diabetic cardiomyopathy (DCM) is one of the primary complications of the cardiovascular system due to diabetes-induced metabolic injury. The present study investigated the autophagy-associated regulatory mechanisms of long non-coding RNAs in cardiac pathological changes in diabetes mellitus (DM). Streptozotocin (STZ)-induced diabetic rats were intramyocardially injected and high concentration glucose (HG)-processed H9C2 cells were infected with growth arrest specific transcript 5 (GAS5)-loaded AAV-9 adenovirus. HG-processed H9C2 cells also underwent transfection with small interfering RNA-p27. Hematoxylin and eosin and Masson staining evaluated myocardial histological changes. Quantitative PCR detected the expression levels of GAS5, fibrosis markers (collagen I, collagen III, TGF-beta and connective tissue growth factor) and microRNA (miR)-221-3p. Western blotting determined the expression levels of autophagy-associated proteins [microtubule-associated proteins 1A/1B light chain 3B (LC3B) I, LC3B II and p62] and p27. Targetscan7.2 was used to predict binding sites between miR-221-3 and p27. Dual luciferase reporter assayed the effect of miR-221-3p on luciferase activity of GAS5 and p27. GAS5 downregulated high blood glucose concentrations in STZ-induced diabetic rats, however its expression levels decreased in both HG-processed H9C2 cells and the myocardium of DM model rats. GAS5 attenuated the histological abnormalities and reversed the decreased LC3B II and increased p62 expression levels of DM model rats. miR-221-3p mimic suppressed the activity of both GAS5-wild-type (WT) and p27-WT. miR-221-3p expression levels were increased in both HG-processed H9C2 and diabetic myocardium. p27 expression levels decreased following HG but were upregulated by GAS5. sip27 abolished the effect of GAS5 on DCM. GAS5 promoted cardiomyocyte autophagy in DCM to attenuate myocardial injury via the miR-221-3p/p27 axis.

Automated summary

The study found that the long non-coding RNA GAS5 promotes cardiomyocyte autophagy via the miR-221-3p/p27 axis to alleviate cardiac damage in diabetic cardiomyopathy.