Dataset Information


MicroRNA-9 inhibits hyperglycemia-induced pyroptosis in human ventricular cardiomyocytes by targeting ELAVL1.

ABSTRACT: Diabetic cardiomyopathy is a common complication in patients with diabetes and is associated with underlying chronic inflammation and cardiac cell death, subsequently leading to heart failure (HF). ELAV-like protein 1 (ELAVL1) plays a critical role in the progression of inflammation and HF. However the role of ELAVL-1 in inflammation induced cardiac cell death (pyroptosis) under hyperglycemic condition remains elusive. Our data demonstrates that ELAVL1 expression augmented with a concomitant increase in caspase-1 and IL-1 beta expression in human hearts and human ventricular cardiomyocytes under hyperglycemic condition. Furthermore, ELAVL1 knockdown abrogates TNF-? induced canonical pyroptosis via NLRP3, caspase-1 and IL-1beta suppression. Bioinformatics analysis and target validation assays showed that miR-9 directly targets ELAVL1. Interestingly, miRNA-9 expression significantly reduced in high glucose treated cardiomyocytes and in human diabetic hearts. Inhibition of miR-9 upregulates ELAVL1 expression and activates caspase-1. Alternatively, treatment with miR-9 mimics attenuates hyperglycemia-induced ELAVL1 and inhibits cardiomyocyte pyroptosis. Taken together our study highlights the potential therapeutic implications of targeting miR-9/ELAVL1 in preventing cardiomyocyte cell loss during HF in diabetics.


PROVIDER: S-EPMC4818978 | BioStudies | 2016-01-01

REPOSITORIES: biostudies

Similar Datasets

1000-01-01 | S-EPMC4237254 | BioStudies
2021-01-01 | S-EPMC7906806 | BioStudies
2019-01-01 | S-EPMC6700436 | BioStudies
2013-01-01 | S-EPMC3756475 | BioStudies
2019-01-01 | S-EPMC6612907 | BioStudies
2018-01-01 | S-EPMC6205728 | BioStudies
2020-01-01 | S-EPMC7327979 | BioStudies
2012-01-01 | S-EPMC3341631 | BioStudies
2015-01-01 | S-EPMC4769861 | BioStudies
2020-01-01 | S-EPMC7046511 | BioStudies