Hsa_circ_0012919 promotes pyroptosis in CD4+T cells of systemic lupus erythematous by miR‐125a‐3p/GSDMD axis.

The etiology of systemic lupus erythematous (SLE) remains unclear. Pyroptosis, a new model of programmed cell death, was poorly explored in the pathogenesis of SLE. We found cell pyroptosis in CD4+T cells of SLE patients and kidneys from MRL/lpr mice by examining caspase‐1 and gasdermin D (GSDMD) in by RT‐PCR, Western blot, and levels of IL‐1β, IL‐18 and TNF‐α were detected by RT‐PCR and Elisa. Expression of caspase‐1 and GSDMD and levels of IL‐1β, IL‐18, TNF‐α decreased significantly after downregulation of hsa_circ_0012919 (p < 0.05). Inhibition of miR‐125a‐3p enhanced expression of caspase‐1 and GSDMD (p < 0.05), and increased the release of IL‐1β, IL‐18 and TNF‐α (p < 0.05), thereby counteracting the effect of hsa_circ_0012919 knockdown on pyroptosis. Finally, we identified GSDMD as the target gene of miR‐125a‐3p. Silencing GSDMD reversed the effect of 5‐aza‐deoxycytidine in increasing release of IL‐1β, IL‐18, TNF‐α and activating caspase‐1, but it could be reversed by miR‐125a‐3p inhibitor. In conclusion, hsa_circ_0012919 regulated the pyroptosis in the CD4+ T cells of SLE patients by miR‐125a‐3p/GSDMD axis. [ABSTRACT FROM AUTHOR]