Abstract：
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.
摘要：
系统性红斑狼疮（SLE）的病因尚不清楚。焦亡,一种新的程序性细胞死亡模型，对SLE的发病机制研究甚少。我们通过RT-PCR检查caspase-1和gasderminD（GSDMD），发现SLE患者的CD4T细胞和MRL/lpr小鼠的肾脏中的细胞焦亡，蛋白质印迹,和IL-1β水平，采用RT-PCR和ELISA法检测IL-18和TNF-α。caspase-1和GSDMD的表达及IL-1β水平,hsa_circ_0012919下调后,IL-18、TNF-α显著降低(p<0.05)。抑制miR-125a-3p可增强caspase-1和GSDMD的表达（p<0.05），并增加IL-1β的释放，IL-18和TNF-α（p<0.05），从而抵消hsa_circ_0012919敲低对焦亡的影响。最后,我们确定GSDMD为miR-125a-3p的靶基因。沉默GSDMD逆转了5-氮杂脱氧胞苷增加IL-1β释放的作用，IL-18，TNF-α和激活的caspase-1，但它可以被miR-125a-3p抑制剂逆转。总之,hsa_circ_0012919通过miR-125a-3p/GSDMD轴调节SLE患者CD4+T细胞的焦亡。
