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

BACKGROUND: Celastrol (Cel) as an anti-inflammatory and anti-apoptotic agent has been corroborated in multiple cell damage models. However, the protective effect of Cel in high glucose (HG)-induced cardiomyocyte injury is still unclear. The present study is performed 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 mM) or HG (30 mM) and then administered with Cel. CCK8 and flow cytometry were used to detect cell proliferative activity and apoptosis. mRNA and protein expression were analyzed using RT-qPCR and western blotting, respectively. Bioinformatics algorithm and luciferase reporter gene assay were utilized 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: Our findings have demonstrated that Cel administration antagonized HG-induced cardiomyocyte apoptosis and inflammation through upregulating Gas6 expression by restraining miR-345-5p.