Journal
CELL CYCLE
Volume 19, Issue 22, Pages 3054-3065Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15384101.2020.1831245
Keywords
GAS5; miR-34b-3p; AHR; NLRP3 inflammasome; pyroptosis; diabetic cardiomyopathy
Categories
Ask authors/readers for more resources
Long noncoding RNA GAS5 is down-regulated in cardiomyocytes in diabetic cardiomyopathy (DCM). Here, we studied the involvement of GAS5 in DCM by analyzing its expression in DCM mouse model and cardiac muscle cell line (HL-1 cells). Compared with normal mice, GAS5 was severely down-regulated in heart tissues of DCM mice. GAS5 overexpression improved cardiac function and myocardial hypertrophy in DCM mice. In addition, the expression of NLRP3, caspase-1, Pro-caspase-1, IL-1 beta and IL-18 were increased in heart tissues of DCM mice and high glucose-treated HL-1 cells, which was repressed by GAS5 up-regulation. GAS5 overexpression suppressed caspase-1 activity, LDH release and the levels of IL-1 beta, IL-18 in the high glucose-treated HL-1 cells. Moreover, GAS5 regulated AHR expression by sponging miR-34b-3p. Furthermore, GAS5 overexpression suppressed NLRP3 inflammasome activation-mediated pyroptosis by regulating miR-34b-3p/AHR axis. In summary, our study demonstrates that GAS5 acts as a competing endogenous RNA to enhance AHR expression by sponging miR-34b-3p, which consequently represses NLRP3 inflammasome activation-mediated pyroptosis to improve DCM. Thus, our data provide a novel lncRNA GAS5 that could be a valuable target for DCM treatment.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available