Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, 650500, People's Republic of China.
Medical School, Kunming University of Science and Technology, Kunming, 650500, People's Republic of China.
Inflamm Res. 2022 Nov;71(10-11):1191-1202. doi: 10.1007/s00011-022-01624-9. Epub 2022 Aug 15.
Gasdermin D (GSDMD) is a cytoplasmic protein that is encoded by the gasdermin family GSDMD gene and is the ultimate executor of pyroptosis. Pyroptosis is a mode of lysis and inflammation that regulates cell death, ultimately leading to cell swelling and rupture. In sepsis, a dysregulated host response to infection frequently results in hyperinflammatory responses and immunosuppression, eventually leading to multiple organ dysfunction. Pyroptosis regulates innate immune defenses and plays an important role in the process of inflammatory cell death, and the absence of any link in the entire pathway from GSDMD to pyroptosis causes bacterial clearance to be hampered. Under normal conditions, the process of pyroptosis occurs much faster than apoptosis, and the threat to the body is also much greater.
We conducted a systematic review of relevant reviews and experimental articles using the keywords sepsis, Gasdermin D, and Pyroptosis in the PubMed, Scopus, Google Scholar, and Web of Science databases.
Combined with the pathogenesis of sepsis, it is not difficult to find that pyroptosis plays a key role in bacterial inflammation and sepsis. Therefore, GSDMD inhibitors may be used as targeted drugs to treat sepsis by reducing the occurrence of pyroptosis. This review mainly discusses the key role of GSDMD in sepsis.
Gasdermin D(GSDMD)是一种细胞质蛋白,由 GSDMD 基因家族编码,是细胞焦亡的最终执行者。细胞焦亡是一种调节细胞死亡的裂解和炎症模式,最终导致细胞肿胀和破裂。在脓毒症中,宿主对感染的失调反应常导致过度炎症反应和免疫抑制,最终导致多器官功能障碍。细胞焦亡调节先天免疫防御,在炎症细胞死亡过程中发挥重要作用,而从 GSDMD 到细胞焦亡的整个途径中的任何一环缺失都会阻碍细菌清除。在正常情况下,细胞焦亡的发生速度比细胞凋亡快得多,对身体的威胁也大得多。
我们使用 PubMed、Scopus、Google Scholar 和 Web of Science 数据库中的关键词脓毒症、Gasdermin D 和细胞焦亡,对相关综述和实验文章进行了系统回顾。
结合脓毒症的发病机制,不难发现细胞焦亡在细菌炎症和脓毒症中起着关键作用。因此,通过减少细胞焦亡的发生,GSDMD 抑制剂可能被用作治疗脓毒症的靶向药物。本综述主要讨论了 GSDMD 在脓毒症中的关键作用。