Blocking GSDME-mediated pyroptosis in renal tubular epithelial cells alleviates disease activity in lupus mice

An increase in apoptosis and/or defects in the clearance of apoptotic cells resulting in massive secondary necrosis have been recognized as the main causes of systemic lupus erythematosus (SLE). Recent findings have revealed that gasdermin E (GSDME)-mediated pyroptosis is a mechanism associated with...

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Published in:Cell death discovery 2022-03, Vol.8 (1), p.113-113, Article 113
Main Authors: Luo, Guihu, He, Yi, Yang, Fangyuan, Zhai, Zeqing, Han, Jiaochan, Xu, Wenchao, Zhang, Jialin, Zhuang, Lili, Zhang, Yanan, Li, Yehao, Song, Rui, Luo, Xiaoqing, Liang, Jianheng, Sun, Erwei
Format: Article
Language:English
Subjects:
631/250/1933
631/250/249/1313/1613
Apoptosis
Biochemistry
Biomedical and Life Sciences
Caspase-3
Cell Biology
Cell Cycle Analysis
Cycloheximide
Epithelial cells
Kidneys
Life Sciences
Lupus
Pristane
Pyroptosis
Renal tubules
Stem Cells
Systemic lupus erythematosus
Tumor necrosis factor-TNF
Tumor necrosis factor-α
Tumors
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Summary:An increase in apoptosis and/or defects in the clearance of apoptotic cells resulting in massive secondary necrosis have been recognized as the main causes of systemic lupus erythematosus (SLE). Recent findings have revealed that gasdermin E (GSDME)-mediated pyroptosis is a mechanism associated with secondary necrosis. We aimed to investigate the effects of GSDME-mediated pyroptosis on disease activity in lupus mice. In vivo, high levels of GSDME expression were observed in the renal tubules of pristane-induced lupus (PIL) mice and SLE patients. In lupus mice, GSDME knockout or SP600125 administration effectively ameliorated lupus-like features by inhibiting GSDME-mediated renal tubular epithelial cell pyroptosis. In vitro, treatment with tumour necrosis factor-α (TNF-α) plus cycloheximide (CHX) or SLE sera induced HK2 cells to undergo pyroptosis in a caspase-3- and GSDME-dependent manner. Likewise, SP600125 significantly reduced GSDME expression and decreased pyroptosis in HK2 cells. GSDME-mediated pyroptosis may be associated with SLE pathogenesis, and targeting GSDME may be a potential strategy for treating SLE.
ISSN:2058-7716
2058-7716
DOI:10.1038/s41420-022-00848-2