Vitronectin in health and disease: Mechanisms and therapeutic implications

Vitronectin (VTN) is a multifunctional glycoprotein abundantly present in plasma and the extracellular matrix. Primarily synthesized by the liver, circulating VTN exists as a monomeric molecule in a folded conformation, where it regulates thrombosis, hemostasis, and fibrinolysis. Under pathological conditions such as trauma or stress, VTN is up-regulated in diverse tissues and deposited into the extracellular matrix as multimeric aggregates, where it mediates cell adhesion, spreading, and migration, the biological processes critical for tissue repair and remodeling. VTN also promotes cell survival and differentiation, underscoring its translational utility in stem cell culture and regenerative medicine. Beyond its physiological roles, VTN emerges as a key modulator of tumor progression, facilitating cancer cell migration and invasion through interactions within the tumor microenvironment. In renal pathophysiology, VTN participates in the formation of the fibrogenic niches in kidney fibrosis and aggravates glomerular injury. VTN is further implicated in infectious diseases and disorders of the central nervous system, cardiovascular system, liver, and lungs, with potential as a diagnostic biomarker in body fluids. This review summarizes current knowledge on VTN's structure, biological functions, and its multifaceted contributions to human diseases, offering insights for therapeutic targeting.