Acute and critical illnesses are typically accompanied by hemodynamic instability, tissue edema, mechanical ventilation and extracellular matrix remodeling.Abnormal shear stress, mechanical stretch, pressure loading and tissue deformation continuously reshape the local mechanical microenvironment.Piezo1 is a mechanosensitive cation channel that converts mechanical stimuli into intracellular signals dominated by ca² + influx and contributes to vascular homeostasis, immune regulation and tissue repair.In sepsis-associated intestinal epithelial injury, pulmonary endothelial mechanical loading and infection-related immune responses, Piezo1-associated ca² + signaling has been implicated in intestinal barrier injury, mitochondrial stress and apoptosis, endothelial barrier disruption or protection, and enhanced host defense.The direction of its effects depends on the cell and experimental context and cannot be determined solely by the intensity or duration of activation.The present review summarizes the fundamental mechanisms of Piezo1-mediated mechanosensing and mechanotransduction in sepsis, acute respiratory distress syndrome, acute kidney injury and trauma/hemorrhagic shock.It also discusses the therapeutic potential and translational challenges of targeting Piezo1.Mechanical alterations in acute and critical illnesses may influence cellular processes, including inflammatory regulation, endothelial barrier function, mitochondrial stress and cell injury, through Piezo1-associated signaling.However, direct evidence and the direction of effects vary between diseases, and shared mechanisms across organs remain to be validated.Defining the cell-specific and stimulusand disease stage-dependent effects of Piezo1 may deepen understanding of organ dysfunction in acute and critical illness and provide a basis for research into interventions targeting mechanical signaling.
