Fibronectin

Fibronectin is a high-molecular-weight glycoprotein of the extracellular matrix and plasma. It exists as soluble plasma fibronectin and insoluble cellular fibronectin that is assembled into fibrillar matrices by cells. Each subunit of fibronectin is about 220-250 kDa and comprises repeating modules of type I, II, and III domains. Two nearly identical polypeptide chains are linked by a disulfide bond near the C-terminus to form a dimer. In humans, alternative splicing of the fibronectin gene yields variants that include the extra domains EDA (EIIIA) and EDB (EIIIB) and the V segment, producing tissue-specific isoforms that are prevalent in development and wound healing.

Fibronectin has multiple binding sites: the RGD sequence in the FNIII9-10 modules binds integrins (for example α5β1 and αv-containing integrins) to promote cell adhesion; other sites bind collagen, heparin, fibrin, and other ECM components. Through these interactions, fibronectin acts as a major organizer of the extracellular matrix and as a bridge between cells and the ECM, supporting adhesion, migration, proliferation, and differentiation. Fibronectin also participates in wound healing and angiogenesis and can be assembled into fibrils by cell-mediated contraction in a process called fibronectin fibrillogenesis.

Fibronectin is synthesized by many cell types; plasma fibronectin is predominantly produced by hepatocytes and circulates in blood, while cellular fibronectin is deposited into the ECM by fibroblasts, epithelial, and endothelial cells. Aberrant expression or splicing of fibronectin is associated with pathological conditions, including fibrosis, tumor progression, and vascular diseases, and it has been explored as a target in various therapies.