Abstract
Fibronectin (FN) is a widely distributed glycoprotein which is present in different bodily fluids, on the surface of cells and in the extracellular matrix (ECM). It plays roles in various processes, including cell adhesion, migration, growth, proliferation, and tissue repair. Fibronectin exists in 2 forms: a soluble, inactive molecule, called plasma FN (pFN), which is synthesized by hepatocytes in the liver, and an insoluble cellular form (cFN), which is produced locally by different types of cells and is a key component of the ECM. Fibrinogen fibrils ensure structural support for cell adhesion and promote cell migration, proliferation and apoptosis. Additionally, FN controls the availability of growth factors. The plasma form of FN is a crucial component of the fibrin clot in the early wound-healing response, while the cellular form of FN supports efficient platelet adhesion, activation, aggregation, and procoagulant activity. Alternative splicing of the FN gene results in the generation of protein variants which contain the additional isoforms - extra domain A of FN (EDA) and extra domain A of FN (EDB); these are associated with, e.g., tissue remodeling, fibroblast differentiation, inflammation, and tumor progression. Fibronectin also serves as a target for a large number of bacterial proteins, and as part of a 3-component bridge (FN, integrin and FN-binding proteins - FnBPs) it contributes to bacterial colonization of endothelial and epithelial cells. Fibronectin has been identified in sepsis in humans as a negative acute-phase protein, and a low level of FN seems to be a marker of a poor prognosis for a patient. Here, the role of FN in inflammatory processes and sepsis is presented.
Highlights
Fibronectin exists in 2 forms: a soluble, inactive molecule, called plasma FN, which is synthesized by hepatocytes in the liver, and an insoluble cellular form, which is produced locally by different types of cells and is a key component of the extracellular matrix (ECM)
Plasma FN is a significant component of fibrin clots, taking part in hemostasis stabilizing the clot structure, provisional matrix formation and the repair process
In addition to the plasma FN, isoforms of cellular FN play a key role in pathology
Summary
Fibronectin is involved in cellular processes such as cell adhesion, migration, growth and survival, and it is required for embryonic development.[1,3] Plasma FN supports hemostasis and regulates thrombosis, and it significantly accelerates healing by limiting the extent of inflammation.[5] As a key component of a fibrin clot, pFN supports hemostasis by being rapidly deposited at the injured vessel wall and by supporting platelet aggregation via pFN–fibrin complexes.[5] The role of cFN is to form and maintain tissue architecture and to regulate cellular processes.[1]
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