胃凋亡是一种裂解炎症编程细胞死亡的形式，被微生物感染或病理刺激（如中风或癌症）引发（在Shi J等人审查2017; Man Sm等人2017; Tang D等人2019;郑z＆li g 2020）。胃泌素的过程保护宿主免受微生物感染，但如果过度激活，也会导致病理炎症。肉肉瘤的形态学特征包括细胞溶胀，细胞膜破裂并将细胞内含量释放到细胞外环境中。腐蛋白还具有染色质缩合的特征，然而这不是糊化症的关键或普遍特征（在Man Sm等人的评论中。2017; Tang D等人2019）。腐蚀性由燃料蛋白家族的蛋白质进行，该植物介导膜毛孔形成（Liu x等人2016; Ding J等，2016; Mulvihill E等，2018; Broz P等人2020）。胃癌可被定义为汽笛介导的编程坏死性细胞死亡（Shi J等，2017; Galluzzi L等人2018）。汽笛（GSDM）超家族（GSDM）包括GSDMA，GSDMB，GSDMC，GSDMD，GSDME（或DFNA5）和PJVK（DFNB59）（KOVACS SB和MAO EA 2018）。每种蛋白质含有N-末端结构域，具有内在的坏死孔形成活性，并且据报道，通过分子内结构域关联抑制细胞死亡的C末端域（Liu X等，2016; Ding J等，2016; Liu Z等人。2018,2019; kuang s等人。2017）。 Proteolytic cleavage in the linker connecting the N‑ and C‑terminal domains of gasdermins releases the C‑terminus, allowing the gasdermin N‑terminus to translocate to the cell membrane and oligomerize to form pores (Shi J et al. 2015; Ding J et al. 2016; Sborgi L et al. 2016; Feng S et al. 2018; Yang J et al. 2018; Mulvihill E et al. 2018). Although PJVK (DFNB59) is included to the gasdermin family, it is not known whether PJVK is cleaved and whether the full length or the N-terminal portion of PJVK is responsible for forming membrane pores. The N‑terminal fragments of GSDMs strongly bind to phosphatidylinositol phosphates and weakly to phosphatidylserine, found on the inner leaflet of the plasma membrane (Liu X et al. 2016; Ding J et al. 2016; Mulvihill E et al. 2018). Gasdermins are also able to target cardiolipin, which is often found in mitochondrial membranes and membranes of bacteria (Liu X et al. 2016; Rogers C et al. 2019). The size of the GSDMD pore is estimated to be 10–20 nm (Ding J et al. 2016; Sborgi L et al. 2016). The pore‑forming activity of GSDMs in the cell membrane facilitates the release of inflammatory molecules such as interleukin (IL)‑1β and IL‑18 (mainly in GSDMD-mediated pyroptosis), and eventually leads to cytolysis in mammalian cells, releasing additional proinflammatory cellular contents including danger signals such as high mobility group box‑1 (HMGB1) (Shi J et al. 2015; He W et al. 2015; Evavold CL et al. 2017; Semino C et al. 2018; Volchuk A et al. 2020). Pyroptosis can occur in immune cells such as macrophages, monocytes and dendritic cells and non‑immune cell types such as intestinal epithelial cells, trophoblasts and hepatocytes (Taabazuing CY et al. 2017; Li H et al. 2019; Jia C et al. 2019). GSDME can be cleaved by caspase‑3 (CASP3) to induce pyroptosis downstream of the “apoptotic” machinery (Wang Y et al. 2017; Rogers C et al. 2017), whereas GSDMD is cleaved by inflammatory CASP1, CASP4 and CASP5 in humans, and CASP1, CASP11 in mice to induce pyroptosis associated with inflammasome activation (Shi J et al. 2015; Kayagaki N et al. 2015). CASP3 cleavage of GSDMD results in its inactivation (Taabazuing et al. 2017). In mouse macrophages, CASP8 can also cleave GSDMD and cause pyroptosis when TAK1 is inhibited (Malireddi R et al. 2018; Orning P et al. 2018; Sarhan J et al. 2018), and TAK1 inhibition also leads to GSDME cleavage (Sarhan J et al. 2018). Furthermore, activated CASP8 can drive inflammasome-independent cleavage of both pro-IL-1β and GSDMD downstream of the extrinsic cell death receptor signaling pathway switching apoptotic signaling to GSDMD-dependent pyroptotic-like cell death (Donado CA et al. 2020). The cleavage and activation of GSDMD in neutrophils is mediated by neutrophil elastase (NE or ELANE), which is released from azurophil granules into the cytosol during neutrophil extracellular trap (NET) formation (Kambara H et al. 2018). Further, granzyme A (GZMA) released from cytotoxic T lymphocytes and natural killer (NK) cells specifically target GSDMB for interdomain cleavage to activate GSDMB-dependent pyroptosis in target tumor cells (Zhou Z et al. 2020). Similarly, granzyme B (GZMB) released from cytotoxic T lymphocytes and natural killer (NK) cells, can induce GSDME‑dependent lytic cell death in tumor targets via the CASP3‑mediated cleavage of GSDME (Zhang Z et al. 2020).

该反应模块描述了GSDMD和GSDME的糊化活性。虽然哺乳动物GSDMA，GSDMB和GSDMC的N末端域也有能力形成毛孔（FENG S等人2018; ROUN J等，2018），它们在诱导糊化症，促炎细胞因子的分泌中的功能在宿主中的杀菌活性仍然待研究，并且不被该反应模块覆盖。