Endoplasmic Reticulum Stress and Critical Care Medicine

Many patients suffer from multiple organ dysfunction syndrome (MODS), which represents a dominant cause of death in the intensive care unit. Current theories about the mechanisms of MODS include inflammation, dysregulated immune response, reduced cellular oxygen utilization, cytopathic hypoxia, and apoptosis. Moreover, an increasing number of studies have shown that endoplasmic reticulum stress (ERS) is related to organ dysfunction. The endoplasmic reticulum is an organelle that is responsible for secretion and membrane protein synthesis and assembly as well as some other physiological activities. Under certain conditions, the homeostasis of ER can be lost, causing the accumulation of unfolded or misfolded protein, which is termed as ERS. During ERS, unfolded protein response (UPR) is activated. Once UPR fails to rebuilt cellular homeostasis, cell function will be impaired and apoptosis will be induced. To better understand the relationship between ERS and severe diseases, we summarize the current research in the context of ERS and UPR signaling associated with various organ dysfunction and severe diseases, including acute lung injury, hepatic injury, heart failure, hemorrhagic shock with multiple organ dysfunction, sepsis, and some other diseases. We also discuss ERS or UPR as a novel therapeutic target and their future directions.