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

• DOI: 10.1038/s41420-022-00848-2
• Publication Date: 2022-03-12T08:05:48Z
• Authors: Guihu Luo; Yi He; Fangyuan Yang; Zeqing Zhai; Jiaochan Han; Wenchao Xu; Jialin Zhang; Lili Zhuang; Yanan Zhang; Yehao Li; Rui Song; Xiaoqing Luo; Jianheng Liang; Erwei Sun
• Keywords: Pyroptosis

An increase in apoptosis and/or defects the clearance of apoptotic cells resulting massive secondary necrosis have been recognized as main causes systemic lupus erythematosus (SLE). Recent findings revealed that gasdermin E (GSDME)-mediated pyroptosis is a mechanism associated with necrosis. We aimed to investigate effects GSDME-mediated on disease activity mice. In vivo, high levels GSDME expression were observed renal tubules pristane-induced (PIL) mice and SLE patients. mice, knockout or SP600125 administration effectively ameliorated lupus-like features by inhibiting tubular epithelial cell pyroptosis. vitro, treatment tumour factor-α (TNF-α) plus cycloheximide (CHX) sera induced HK2 undergo caspase-3- GSDME-dependent manner. Likewise, significantly reduced decreased cells. may be pathogenesis, targeting potential strategy for treating SLE.