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. 2023 Aug;54(4):313-327.
doi: 10.1007/s10735-023-10135-8. Epub 2023 Jun 21.

Knockdown of USF2 inhibits pyroptosis of podocytes and attenuates kidney injury in lupus nephritis

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Knockdown of USF2 inhibits pyroptosis of podocytes and attenuates kidney injury in lupus nephritis

Ying Xie et al. J Mol Histol. 2023 Aug.

Abstract

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.

Keywords: Lupus nephritis; Podocyte injury; Pyroptosis; Upstream stimulatory factor 2.

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