MicroRNA-30d regulates cardiomyocyte pyroptosis by directly targeting foxo3a in diabetic cardiomyopathy

• DOI: 10.1038/cddis.2014.430
• Publication Date: 2014-10-23T13:17:31Z
• Authors: X Li; N Du; Q Zhang; J Li; X Chen; X Liu; Y Hu; W Qin; N Shen; C Xu; Z Fang; Y Wei; R Wang; Z Du; Y Zhang; Y Lu
• Keywords: Pyroptosis; Diabetic Cardiomyopathy; Proinflammatory cytokine

Diabetic cardiomyopathy is a common cardiac condition in patients with diabetes mellitus, which can result hypertrophy and subsequent heart failure, associated pyroptosis, the pro-inflammatory programmed cell death. MicroRNAs (miRNAs), small endogenous non-coding RNAs, have been shown to be involved diabetic cardiomyopathy. However, whether miRNAs regulate pyroptosis remains unknown. Our study revealed that mir-30d expression was substantially increased streptozotocin (STZ)-induced rats high-glucose-treated cardiomyocytes as well. Upregulation of promoted cardiomyocyte cardiomyopathy; conversely, knockdown attenuated it. In an effort understand signaling mechanisms underlying pro-pyroptotic property mir-30d, we found forced upregulated caspase-1 cytokines IL-1β IL-18. Moreover, directly repressed foxo3a its downstream protein, apoptosis repressor caspase recruitment domain (ARC). Furthermore, silencing ARC by siRNA mimicked action mir-30d: upregulating inducing pyroptosis. These findings us propose new pathway leading under hyperglycemic conditions: mir-30d↑→foxo3a↓→ ARC↓→caspase-1↑→IL-1β, IL-18↑→pyroptosis↑. Therefore, may promising therapeutic target for management