As an essential factor in the prognosis of Systemic lupus erythematosus (SLE), lupus nephritis (LN) can accelerate the rate at which patients with SLE can transition to chronic kidney disease or even end-stage renal disease (ESRD). Proteinuria due to decreased glomerular filtration rate following podocyte injury is LN’s most common clinical manifestation. Podocyte pyroptosis and related inflammatory factors in its process can promote lupus to involve kidney cells and worsen the occurrence and progression of LN, but its regulatory mechanism remains unknown. Accumulating evidence has shown that upstream stimulatory factor 2 (USF2) plays a vital role in the pathophysiology of kidney diseases. In this research, multiple experiments were performed to investigate the role of USF2 in the process of LN. USF2 was abnormally highly expressed in MRL/lpr mice kidney tissues. Renal function impairment and USF2 mRNA levels were positively correlated. Silencing of USF2 in MRL/lpr serum-stimulated cells significantly reduced serum-induced podocyte pyroptosis. USF2 enhanced NLRP3 expression at the transcriptional level. Silencing of USF2 in vivo attenuated kidney injury in MRL/lpr mice, which suggests that USF2 is important for LN development and occurrence.

作为系统性红斑狼疮（SLE）预后的重要因素，狼疮性肾炎（LN）可以加快SLE患者向慢性肾脏病甚至终末期肾病（ESRD）转变的速度。足细胞损伤后肾小球滤过率降低导致的蛋白尿是 LN 最常见的临床表现。足细胞焦亡及其过程中相关炎症因子可促进狼疮累及肾细胞，加重LN的发生和进展，但其调控机制尚不清楚。越来越多的证据表明上游刺激因子 2 (USF2) 在肾脏疾病的病理生理学中发挥着至关重要的作用。在本研究中，进行了多项实验来研究USF2在LN过程中的作用。USF2 在 MRL/lpr 小鼠肾组织中异常高表达。肾功能损害与USF2 mRNA水平呈正相关。在MRL/lpr血清刺激的细胞中沉默USF2可显着减少血清诱导的足细胞焦亡。USF2 在转录水平上增强了 NLRP3 的表达。体内 USF2 沉默可减轻 MRL/lpr 小鼠的肾损伤，这表明 USF2 对于 LN 的发育和发生很重要。