Gsdme, also known as Gasdermin E, is a crucial component of the gasdermin family proteins. It plays a key role in the process of pyroptosis, a type of gasdermin-mediated cell death. The caspase-3/Gsdme signal pathway acts as a switch between apoptosis and pyroptosis in cancer cells [2,4]. When Gsdme is highly expressed and cleaved by active caspase-3, it releases the N-terminal domain to form pores in the cell membrane, leading to pyroptosis. Gsdme-related research often utilizes gene knockout (KO) mouse models to explore its functions in vivo.

In atherosclerosis, ApoE and Gsdme dual-deficiency mice showed a reduction in atherosclerotic lesion area and inflammatory response when fed a high-fat diet, indicating that Gsdme-mediated pyroptosis promotes the progression of atherosclerosis [1]. In obstructive nephropathy, deletion of Caspase-3 or Gsdme alleviated renal tubule damage, inflammation, and the development of hydronephrosis and kidney fibrosis after ureteral obstruction, suggesting that Gsdme-mediated pyroptosis in renal parenchymal cells contributes to the disease process [3]. In hepatocellular carcinoma, suppression of Gsdme expression in non-tumor cells decreased the proportion of M2-like macrophages in the tumor microenvironment and enhanced the cytotoxicity of CD8 + T cells [5].

In conclusion, Gsdme is essential in regulating pyroptosis and has a significant impact on various disease conditions such as atherosclerosis, obstructive nephropathy, and hepatocellular carcinoma. The use of Gsdme KO mouse models has been instrumental in uncovering its role in these diseases, providing potential therapeutic targets for treatment.