MiRNA-1 promotes pyroptosis of cardiomyocytes and release of inflammatory factors by downregulating the expression level of PIK3R1 through the FoxO3a pathway.

Abstract

Pyroptosis can be seen in both physiological and pathological processes, and whether it plays a positive or negative role has not been fully clarified, especially in the study of cardiology, which deserves more attention. A model of cardiomyocyte Hypoxia/Reoxygenation was established to detect MicroRNA (miRNA) expression. The C57BL/6 mice and H9c2 cells were respectively treated with Ischemic/Reperfusion (I/R) and Hypoxia/Reoxygenation (H/R). Then, the concentrations of interleukin-1β (IL-1β) and IL-18 were detected in serum and culture medium supernatant, as well as the expression levels of FOXO3, Caspase1, and PIK3R1. In I/R group, the concentrations of IL-1β and IL-18 in the supernatant of H9c2 cell culture solution were significantly higher compared with the control group. Consistent with the supernatant concentrations of IL-1β and IL-18, IL-1β, and IL-18 were also increased at a high level in I/R group at the transcriptional level. Furthermore, the in vitro experiments showed that FOXO3 and Caspase1 were significantly upregulated in myocardial cells with the treatment of I/R group compared to sham group. Concerning pyroptosis, the expression of PIK3R1 was dramatically decreased and the expression of miRNA-1 was significantly increased in H9c2 cells. MiRNA-1 promoted pyroptosis of cardiomyocytes and release of inflammatory factors by downregulating the expression level of PIK3R1.