Chen Meng-Yan, Liu Yang, Fang Min
School of Life Sciences, Henan University, Kaifeng 475004, China.
Henan Key Laboratory of Synthetic Biology and Biomanufacturing, Henan University, Kaifeng 475004, China.
Cells. 2025 Jul 2;14(13):1012. doi: 10.3390/cells14131012.
Sepsis is a life-threatening condition characterized by a dysregulated host response to infection, with complex pathophysiological mechanisms. As an important post-translational modification, protein ubiquitination exhibits multiple non-traditional functions in sepsis beyond its conventional role in protein degradation. Regulating the network of inflammatory cytokines, the dynamic balance of immune cells and organ-specific protective pathways is deeply involved in the pathological process of sepsis. This review focuses on the unconventional roles of protein ubiquitination in sepsis, including its regulation of the inflammatory response, immune cell functions, and organ protection. It systematically summarizes the regulatory mechanisms of ubiquitination in the non-degradative activation of the nuclear factor kappa B (NF-κB) signaling pathway, the dynamic assembly of the NLRP3 inflammasome, the reprogramming of macrophage polarization, and the injuries of organs such as the heart, liver, and lungs. These processes demonstrate that ubiquitination serves as a pivotal nexus between immunological dysregulation and multi-organ impairment in sepsis. This review suggests that targeting non-degradative ubiquitination alterations may provide viable therapeutic options to mitigate excessive inflammation and organ failure in sepsis.
脓毒症是一种危及生命的疾病，其特征是宿主对感染的反应失调，病理生理机制复杂。作为一种重要的翻译后修饰，蛋白质泛素化在脓毒症中除了其在蛋白质降解中的传统作用外，还表现出多种非传统功能。调节炎性细胞因子网络、免疫细胞的动态平衡和器官特异性保护途径，都深度参与了脓毒症的病理过程。本综述重点关注蛋白质泛素化在脓毒症中的非常规作用，包括其对炎症反应、免疫细胞功能和器官保护的调节。它系统地总结了泛素化在核因子κB（NF-κB）信号通路的非降解性激活、NLRP3炎性小体的动态组装、巨噬细胞极化的重编程以及心脏、肝脏和肺等器官损伤中的调控机制。这些过程表明，泛素化是脓毒症免疫失调和多器官损伤之间的关键连接点。本综述表明，针对非降解性泛素化改变可能为减轻脓毒症中的过度炎症和器官衰竭提供可行的治疗选择。
