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

Eur Rev Med Pharmacol Sci. 2020 Nov;24(21):11243-11250. doi: 10.26355/eurrev_202011_23613.

Abstract

Objective: 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.

Materials and methods: 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.

Results: 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.

Conclusions: MiRNA-1 promoted pyroptosis of cardiomyocytes and release of inflammatory factors by downregulating the expression level of PIK3R1.

MeSH terms

  • Animals
  • Cell Hypoxia
  • Cells, Cultured
  • Class Ia Phosphatidylinositol 3-Kinase / genetics*
  • Class Ia Phosphatidylinositol 3-Kinase / metabolism
  • Down-Regulation*
  • Forkhead Box Protein O3 / metabolism*
  • Interleukin-18 / metabolism
  • Interleukin-1beta / metabolism
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Myocytes, Cardiac / metabolism
  • Pyroptosis
  • Rats

Substances

  • FOXO3 protein, rat
  • Forkhead Box Protein O3
  • FoxO3 protein, mouse
  • IL1B protein, mouse
  • IL1B protein, rat
  • Interleukin-18
  • Interleukin-1beta
  • MIRN1 microRNA, rat
  • MicroRNAs
  • Mirn1 microRNA, mouse
  • Class Ia Phosphatidylinositol 3-Kinase
  • Pik3r1 protein, mouse