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.
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The current work was supported by the Natural Science Foundation of Guizhou Province, China (QianKeHeJiChu-ZK [2022] General 409), the Youth Talent Development Project of Guizhou Education Department (Qian Jiao He [2021]177), and the Science and Technology Foundation of Guizhou Provincial Health Commission (gzwkj2021-378).
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The main experiments were performed by Ying Xie, Xiaoying Li, and Wenli Deng, and the manuscript was written by Ying Xie. Nan Nan, Gong Lei, and Min Chen helped with the cell experiments. Jie Yu, Huimei Zou and Peilei Chen collected animal specimens and performed experiments. Daolin Cui and Fan Zhang revised the article and accept responsibility for its content.
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Xie, Y., Li, X., Deng, W. et al. Knockdown of USF2 inhibits pyroptosis of podocytes and attenuates kidney injury in lupus nephritis. J Mol Histol 54, 313–327 (2023). https://doi.org/10.1007/s10735-023-10135-8
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DOI: https://doi.org/10.1007/s10735-023-10135-8