Silencing lncRNA GAS5 alleviates apoptosis and fibrosis in diabetic cardiomyopathy by targeting miR-26a/b-5p

Background LncRNA GAS5 is associated with high glucose-induced cardiomyocyte injury, but its role in diabetic cardiomyopathy (DCM) remains unclear. Methods Mice were administered with streptozotocin to construct the diabetic model (DM). Primary mouse cardiomyocytes were isolated and treated with 30 mmol/L high glucose to mimic the diabetic condition in vitro. GAS5 expression was detected by quantitative reverse transcription polymerase chain reaction. The relationship between GAS5 and miR-26a/b-5p was determined by bioinformatic prediction, luciferase reporter assay and RNA immunoprecipitation assay. The cardiac function of diabetic mice was evaluated by two-dimensional echocardiography. Results GAS5 was significantly upregulated in diabetic cardiomyopathy both in vitro and in vivo. GAS5 knockdown and miR-26a/b-5p overexpression not only effectively attenuated myocardial fibrosis of diabetic mice in vivo but also inhibited high glucose-induced cardiomyocyte injury in vitro. miR-26a/b-5p was identified as a target of GAS5. GAS5 knockdown efficiently attenuated myocardial fibrosis and high glucose-induced cardiomyocyte injury through negatively regulating miR-26a/b-p. Conclusion Our study showed that GAS5 promotes DCM progression by regulating miR-26a/b-5p, suggesting that GAS5 might be a potential therapeutic target for DCM.

Automated summary

The study revealed that GAS5 is upregulated in diabetic cardiomyopathy and promotes DCM progression by regulating miR-26a/b-5p. Knockdown of GAS5 can alleviate myocardial fibrosis and high glucose-induced cardiomyocyte injury. This suggests that GAS5 may be a potential therapeutic target for DCM.