Celastrol mitigates high glucose‐induced inflammation and apoptosis in rat H9c2 cardiomyocytes via miR‐345‐5p/growth arrest‐specific 6

Abstract Background Celastrol (Cel) has been corroborated as an anti‐inflammatory and anti‐apoptotic agent in multiple cell damage models. However, the protective effect of Cel in high glucose (HG)‐induced cardiomyocyte injury is still unclear. The present study aimed to determine whether Cel can mitigate HG‐stimulated cardiomyocyte injury via regulating the miR‐345‐5p/growth arrest‐specific 6 (Gas6) signaling pathway. Methods Cardiomyocytes were exposed to normal glucose (NG; 5 mmol/l) or HG (30 mmol/l) and then administered with Cel. Cell counting kit‐8 and flow cytometry assays were used to detect cell proliferative activity and apoptosis. mRNA and protein expression were analyzed using a quantitative reverse transcriptase‐polymerase chain reaction and western blotting, respectively. A bioinformatics algorithm and a luciferase reporter gene assay were used to determine whether Gas6 is a direct target of miR‐345‐5p. Results The present study confirmed the inhibitory effects of Cel in HG‐induced inflammation in cardiomyocytes. Moreover, Cel exhibited the ability to antagonize HG‐induced cardiomyocyte apoptosis and suppress the elevated Bax/Bcl‐2 ratio elicited by HG stimulation. Intriguingly, Cel treatment revoked the HG‐triggered repression of Gas6 protein expression, and Gas6 loss‐of‐function accelerated HG‐induced cardiomyocyte apoptosis. HG‐triggered up‐regulation of miR‐345‐5p expression was depressed following Cel treatment. Importantly, we validated that Gas6 is a direct target of miR‐345‐5p. Transfection with miR‐345‐5p inhibitors restrained HG‐induced release of pro‐inflammatory cytokines and cell apoptosis. Conclusions The findings of the present study demonstrate that Cel administration antagonized HG‐induced cardiomyocyte apoptosis and inflammation through up‐regulating Gas6 expression by restraining miR‐345‐5p.