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Caspase-1/-11 participates in LPS-induced sepsis-associated acute kidney injury by cleaving GSDMD

ZHAI Bin¹, MA Li-Sha¹, SHEN Rui-Qin¹, YU Jian¹, TAO Yi-Nan², XU Ai-Ping¹, SHAO De-Cui^1,*

¹Cell Electrophysiology Laboratory, Wannan Medical College, Wuhu 241002, China；²Human Anatomy Experiment and Training Center, Wannan Medical College, Wuhu 241002, China

Abstract

The present study was aimed to investigate whether Gasdermin D (GSDMD)-mediated pyroptosis participated in lipopolysaccharide (LPS)-induced sepsis-associated acute kidney injury (AKI), and to explore the role of caspase-1 and caspase-11 pyroptosis pathways in this process. The mice were divided into four groups: wild type (WT), WT-LPS, GSDMD knockout (KO) and KO-LPS. The sepsis-associated AKI was induced by intraperitoneal injection of LPS (40 mg/kg). Blood samples were taken to determine the concentration of creatinine and urea nitrogen. The pathological changes of renal tissue were observed via HE staining. Western blot was used to investigate the expression of pyroptosis-associated proteins. The results showed that the concentrations of serum creatinine and urea nitrogen in the WT-LPS group were significantly increased, compared with those in the WT group (P < 0.01); whereas serum creatinine and urea nitrogen in the KO-LPS group were significantly decreased, compared with those in the WT-LPS group (P < 0.01). HE staining results showed that LPS-induced renal tubular dilatation was mitigated in GSDMD KO mice. Western blot results showed that LPS up-regulated the protein expression levels of interleukin-1β (IL-1β), GSDMD and GSDMD-N in WT mice. GSDMD KO significantly down-regulated the protein levels of IL-1β, caspase-11, pro-caspase-1, caspase-1(p22) induced by LPS. These results suggest that GSDMD-mediated pyroptosis is involved in LPS-induced sepsis-associated AKI. Caspase-1 and caspase-11 may be involved in GSDMD cleavage.

Key words: acute kidney injury; lipopolysaccharide; Gasdermin D; pyroptosis

Received: 　　Accepted:

Corresponding author: 邵德翠　　E-mail:

DOI: 10.13294/j.aps.2023.0012

Citing This Article：

ZHAI Bin, MA Li-Sha, SHEN Rui-Qin, YU Jian, TAO Yi-Nan, XU Ai-Ping, SHAO De-Cui. Caspase-1/-11 participates in LPS-induced sepsis-associated acute kidney injury by cleaving GSDMD. Acta Physiol Sin 2023; 75 (1): 10-16 (in Chinese with English abstract).