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

作者：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^*

来源：Cell Death Discovery, 2022, 8(1): 113.

DOI：10.1038/s41420-022-00848-2

• BALB/C MICE
• JNK
• ERYTHEMATOSUS
• APOPTOSIS
• DEATH
• DFNA5
• ACTIVATION
• MANAGEMENT
• INDUCTION
• NEPHRITIS

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-alpha (TNF-alpha) 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.

• 单位
  南方医科大学