Gsdme, also known as Gasdermin E, is a crucial component of the gasdermin family proteins. It has the ability to convert caspase-3-mediated apoptosis to pyroptosis, a type of inflammatory programmed cell death. The caspase-3/Gsdme signal pathway acts as a switch between apoptosis and pyroptosis, and Gsdme is involved in many biological processes, especially those related to inflammation and cell death regulation [2,4].

In atherosclerosis, ApoE and GSDME dual-deficiency mice showed a reduction of atherosclerotic lesion area and inflammatory response when on 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, suggesting that Gsdme-mediated pyroptosis contributes to the initiation of ureteral obstruction-induced renal tubule injury [3]. In hepatocellular carcinoma, the suppression of Gsdme expression in nontumor 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 a key regulator in the switch between apoptosis and pyroptosis. Gene knockout mouse models have revealed its significant roles in diseases such as atherosclerosis, obstructive nephropathy, and hepatocellular carcinoma, highlighting its potential as a therapeutic target for these diseases.

References:

1. Wei, Yuanyuan, Lan, Beidi, Zheng, Tao, Yuan, Zuyi, Wu, Yue. 2023. GSDME-mediated pyroptosis promotes the progression and associated inflammation of atherosclerosis. In Nature communications, 14, 929. doi:10.1038/s41467-023-36614-w. https://pubmed.ncbi.nlm.nih.gov/36807553/

2. Jiang, Mingxia, Qi, Ling, Li, Lisha, Li, Yanjing. 2020. The caspase-3/GSDME signal pathway as a switch between apoptosis and pyroptosis in cancer. In Cell death discovery, 6, 112. doi:10.1038/s41420-020-00349-0. https://pubmed.ncbi.nlm.nih.gov/33133646/

3. Li, Yinshuang, Yuan, Ying, Huang, Zhong-Xing, Mak, Tak W, Xu, Yanfang. 2021. GSDME-mediated pyroptosis promotes inflammation and fibrosis in obstructive nephropathy. In Cell death and differentiation, 28, 2333-2350. doi:10.1038/s41418-021-00755-6. https://pubmed.ncbi.nlm.nih.gov/33664482/

4. Bhat, Asif Ahmad, Thapa, Riya, Afzal, Obaid, Dua, Kamal, Gupta, Gaurav. 2023. The pyroptotic role of Caspase-3/GSDME signalling pathway among various cancer: A Review. In International journal of biological macromolecules, 242, 124832. doi:10.1016/j.ijbiomac.2023.124832. https://pubmed.ncbi.nlm.nih.gov/37196719/

5. Chen, Shiping, Zhang, Peiling, Zhu, Guiqi, Fan, Jia, Dai, Zhi. 2024. Targeting GSDME-mediated macrophage polarization for enhanced antitumor immunity in hepatocellular carcinoma. In Cellular & molecular immunology, 21, 1505-1521. doi:10.1038/s41423-024-01231-0. https://pubmed.ncbi.nlm.nih.gov/39496854/