Fibronectin is a large protein found throughout the body, playing a widespread role in various biological processes. It is a fundamental component of the extracellular matrix (ECM), the complex network of proteins and other molecules that surround and support cells in tissues. Fibronectin contributes to the structural integrity and proper functioning of organs and tissues, and is involved in many cellular activities.
Understanding Fibronectin
Fibronectin is a large glycoprotein, meaning it is a protein with attached carbohydrate chains. It has a high molecular weight, typically ranging from 500 to 600 kilodaltons (kDa). This protein is composed of two nearly identical subunits linked together by disulfide bonds. These subunits contain repeating sequences, forming distinct functional domains that allow fibronectin to interact with various molecules.
There are two primary forms of fibronectin: plasma fibronectin and cellular fibronectin. Plasma fibronectin is a soluble form that circulates in the blood and other bodily fluids. It is primarily produced by liver cells, known as hepatocytes. Cellular fibronectin, in contrast, is an insoluble form that is a major component of the extracellular matrix. It is secreted by various cell types, including fibroblasts, endothelial cells, chondrocytes, and muscle cells, and then assembled into an insoluble matrix.
Essential Functions of Fibronectin
Fibronectin performs a variety of functions. A primary role involves cell adhesion, where it helps cells attach to the extracellular matrix. Fibronectin binds to specific cell surface receptors called integrins, which then connect to the cell’s internal cytoskeleton, forming structures called focal adhesions. This interaction enables cells to anchor themselves within tissues.
Fibronectin also serves as a guide for cell movement, or cell migration. It provides a “track” or substrate along which cells can move, a process that is important during embryonic development and tissue repair. This movement involves a coordinated interplay between fibronectin, integrins, and the cell’s internal cytoskeleton.
In wound healing and tissue repair, fibronectin plays a significant role. In the initial stages of injury, plasma fibronectin is deposited at the wound site, contributing to the formation of blood clots by cross-linking with fibrin, which helps stop bleeding. This provisional matrix then provides a scaffold for the migration and proliferation of cells involved in healing, such as fibroblasts and endothelial cells, supporting the growth of new tissue.
Fibronectin is additionally important in tissue development and organization. It guides cell differentiation and tissue formation during growth, helping to organize the extracellular matrix into specific structures. The assembly of fibronectin into viscoelastic fibrils acts as a provisional extracellular matrix during embryonic development, influencing the arrangement of other matrix proteins and guiding cell behavior.
Fibronectin’s Role in Health and Illness
Abnormal levels or forms of fibronectin can contribute to various health conditions. In cancer, fibronectin plays a complex role in tumor growth, spread, and angiogenesis. Overexpression of fibronectin is associated with increased cancer cell adhesion and motility, and it can facilitate tumor cell migration and invasion into surrounding tissues. Fibronectin also promotes angiogenesis, which is necessary for tumors to grow and metastasize.
Fibronectin also contributes to fibrotic diseases, characterized by excessive scar tissue formation. In conditions like liver fibrosis or pulmonary fibrosis, there is an abnormal accumulation and deposition of fibronectin and other extracellular matrix proteins. This excessive fibronectin deposition provides a scaffold for further matrix accumulation, disrupting normal tissue architecture and function.
Fibronectin is involved in the inflammatory response and can contribute to tissue damage. Changes in fibronectin’s structure or organization can lead to the release of pro-inflammatory cytokines, activating immune cells and potentially exacerbating inflammation. This can create a feedback loop where increased fibronectin promotes further inflammation.
In cardiovascular disease, fibronectin is linked to conditions affecting the heart and blood vessels, such as atherosclerosis. Fibronectin is an abundant component of the extracellular matrix in atherosclerotic plaques, and its abnormal expression or processing can influence the stability of these lesions.
Therapeutic and Research Applications of Fibronectin
Understanding fibronectin’s functions has led to various applications in medical research and therapeutic strategies. Fibronectin is incorporated into biomaterials and scaffolds for tissue engineering and regenerative medicine. These biomaterials can mimic the natural extracellular matrix, providing a supportive environment for cell growth, adhesion, and differentiation, which is important for repairing damaged tissues or growing new ones.
Researchers are also exploring fibronectin’s use in drug delivery systems. Certain isoforms of fibronectin are often re-expressed in tumors but are largely absent in normal adult tissues. These forms can be targeted to deliver anti-cancer drugs, cytokines, or radioisotopes directly to tumor cells, aiming to increase therapeutic effectiveness while reducing harm to healthy cells.
Fibronectin is also being investigated in biomarker research. Changes in its levels or specific forms can indicate the presence or progression of certain diseases, suggesting its potential as a diagnostic or monitoring tool.
Researchers are exploring ways to modulate fibronectin activity as a therapeutic target. This involves developing strategies to either inhibit or enhance fibronectin’s interactions to treat diseases where its function is abnormal. Such approaches could address conditions like cancer, where fibronectin promotes tumor progression, or fibrotic diseases, where its excessive deposition contributes to scarring.