Department of Pathophysiology, Guizhou Medical University, Guiyang, 550025, China.
Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases, Guizhou Medical University, Guiyang, 550025, China.
J Mol Histol. 2023 Aug;54(4):313-327. doi: 10.1007/s10735-023-10135-8. Epub 2023 Jun 21.
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）预后的一个重要因素，狼疮肾炎（LN）可加速 SLE 患者向慢性肾脏病甚至终末期肾病（ESRD）转变的速度。足细胞损伤导致肾小球滤过率下降引起的蛋白尿是 LN 最常见的临床表现。足细胞焦亡及其过程中的相关炎症因子可促进狼疮累及肾脏细胞，加重 LN 的发生和进展，但具体的调控机制尚不清楚。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起着至关重要的作用。本研究通过多项实验来探究 USF2 在 LN 过程中的作用。在 MRL/lpr 小鼠的肾脏组织中，USF2 异常高表达，且肾功能损伤与 USF2 mRNA 水平呈正相关。在 MRL/lpr 血清刺激的细胞中沉默 USF2 可显著减少血清诱导的足细胞焦亡。USF2 可在转录水平上增强 NLRP3 的表达。体内沉默 USF2 可减轻 MRL/lpr 小鼠的肾脏损伤，这表明 USF2 对 LN 的发生和发展很重要。
