p38 protein as a therapeutic target for sepsis-induced organ dysfunction

Sepsis is a systemic disorder with a dysregulated host response caused by infection and is associated with multiple organ dysfunction and a high risk of mortality. Several factors are involved in the complex pathophysiological process of sepsis, including the inflammatory response, immune response, mitochondrial dysfunction, and coagulation cascade. p38 proteins, a class of mitogen-activated protein kinases, play key roles in inflammatory/immune responses and are involved in essential cellular processes. Previous studies have shown that p38 is highly expressed in sepsis and sepsis-induced organ damage and is involved in complex biological, signaling-driven processes. Therefore, this review aims to summarize the efficacy and mechanism of action of p38 in treating sepsis and sepsis-induced multiple-organ damage. First, the basic structure, signal transduction mechanism of p38, and its role in the pathological process of sepsis are comprehensively described. Second, the mechanism of p38 in sepsis-induced multiple-organ damage (including the heart, liver, lung, and brain) is described. Finally, the discovery and application of p38 inhibitors and the role of p38 in sepsis is discussed. This review provides a new therapeutic target for sepsis-induced multiple-organ dysfunction.