Fibronectin is a dimer composed of two nearly identical subunits, each approximately 250 kDa in size . These subunits are linked covalently near their C-termini by a pair of disulfide bonds. Each monomer consists of three types of repeating units: type I, type II, and type III repeats . The protein can exist in multiple forms due to alternative splicing of a single pre-mRNA, which can generate as many as 20 variants in human fibronectin . This splicing occurs in several regions, including the EDA and EDB domains, which are highly expressed during fibrosis and cancer development .
Fibronectin is involved in a wide variety of cellular interactions with the extracellular matrix (ECM) and plays important roles in cell adhesion, migration, growth, and differentiation . It is critically important in vertebrate development, as demonstrated by the early embryonic lethality of mice with targeted inactivation of the fibronectin gene . In rats, fibronectin is synthesized by various cell types, including fibroblasts, endothelial cells, and certain cancer cells .
Fibronectin is widely expressed in multiple tissues and organs. Plasma fibronectin is synthesized by hepatocytes and exists in a compact, inactive conformation in the bloodstream . It is a major component of fibrin clots and plays a significant role in wound healing. Cellular fibronectin isoforms are synthesized by fibroblasts, endothelial cells, and many types of cancer cells .
The expression and function of fibronectin are regulated by various factors, including growth factors, cytokines, and mechanical stress. Fibronectin binds to distinct ECM components such as collagens, growth factors, and cell surface integrins to carry out its functions . The protein undergoes conformational changes upon binding to integrins or other cell surface receptors, exposing its functional domains and activating extracellular matrix assembly .
Fibronectin has been implicated in many essential biological processes, including tissue repair, fibrosis, and tumor development . The EDA and EDB isoforms of fibronectin are particularly highly expressed during fibrosis and cancer development, making them potential diagnostic and therapeutic targets . Understanding the role of fibronectin in these processes can provide insights into the development of new treatments for various diseases.