Galectin-3 in sepsis: A multifaceted regulator of innate immunity, vascular dysfunction, and organ injury.

Sepsis is a life-threatening syndrome characterized by dysregulated host responses, endothelial injury, microcirculatory disturbance, and progressive organ dysfunction. Galectin-3 (Gal-3), a β-galactoside-binding lectin with diverse intracellular and extracellular activities, has emerged as an important mediator in inflammatory and fibrotic diseases. Increasing evidence suggests that Gal-3 is involved in multiple pathophysiological processes relevant to sepsis, rather than acting within a single pathway. In this review, we summarize the structural and functional features of Gal-3 and discuss its roles in the pathobiology of sepsis, with emphasis on innate immune activation, macrophage and neutrophil responses, inflammasome-related injury, endothelial dysfunction, immunothrombosis, extracellular matrix remodeling, and organ damage. Current studies indicate that Gal-3 can amplify inflammatory signaling, promote leukocyte recruitment and trafficking, modulate phagocyte function, and contribute to vascular barrier impairment and microvascular failure. In addition, Gal-3 appears to participate in post-inflammatory tissue remodeling and fibrosis, suggesting a broader role in the transition from acute injury to maladaptive repair. Beyond its mechanistic relevance, circulating Gal-3 has shown potential as an adjunctive biomarker for disease severity assessment, organ injury stratification, and short-term prognosis, although its specificity and clinical utility remain to be fully established. Emerging experimental evidence also supports Gal-3 as a therapeutic target in sepsis, but its context-dependent and compartment-specific functions require further clarification. Overall, Gal-3 represents a multifunctional molecule that links immune dysregulation, vascular injury, and tissue remodeling in sepsis and may provide new opportunities for biomarker development and mechanism-based intervention.