Fibronectin and liver disease

Abstract

Fibronectin is a glycoprotein found in the extracellular space of most tissues (1-4). It occurs in soluble and insoluble forms. The concentration of fibronectin in circulating plasma is quite high, approximately 30 mg per dl. Fibronectin is also found in amniotic fluid, seminal fluid, joint fluid, cerebrospinal fluid and conditioned medium of many cell types in culture, including hepatocytes (5). Insoluble fibronectin is a component of fibrillar extracellular structures and basal lamina of all tissues with the possible exception of the nervous system.Fibronectin interacts with cells and a number of macromolecules, including fibrin, gelatin and collagen (1-4). Cells specifically adhere to fibronectin and thus use fibronectin to position themselves and move about. Cells also assemble fibronectin into thin extracellular fibrils. Fibronectin in these fibrils is covalently linked together by disulfide bonds and, therefore, is highly insoluble. The fibrils probably serve as a scaffolding to support cell adhesion and movement and also as a nidus for deposition of other connective tissue elements. During blood coagulation, plasma fibronectin is covalently incorporated into the fibrin clot by coagulation Factor XI11 (plasma transglutaminase). Plasma fibronectin has been shown to be an important determinant of the rate of clearance of particulate debris from the circulation and thus is considered to be the major "nonspecific opsonin" of plasma.Soluble fibronectin is composed of two subunits that are approximately 2,250 amino acid residues long and contain 5% carbohydrate. Analyses of amino acid and/ or cDNA sequences indicate that fibronectin is the paradigm of a modular protein (1); more than 90% of the sequence is composed of three different types of homologous units called I, I1 or I11 (Figure 1). There is only one gene for fibronectin, composed of more than 45 exons (coding sequences) and introns (sequences which are removed by splicing during maturation of the mRNA The sequence arginine-glycine-aspartate (RGD) in the tenth block of Type 111 homology seems to be very important for cell adhesion (4). Small peptides with the RGD sequence inhibit cell adhesion, probably by binding to and blocking a specific receptor on the surface of adhering cells. Several kinds of evidence indicate that the adhesion receptor for fibronectin on adhering cells is composed of two integral membrane glycoproteins of molecular weight 140,000. Recent studies indicate that the adhesion receptor for fibronectin is a member of a family of adhesion receptors. Thus, the adhesion receptor for vitronectin, (the other major adhesive protein of blood plasma, but that is another story . . .) is composed of integral membran glycoproteins which also have molecular weights of roughly 140,000, but are different from the glycoproteins of the fibronectin receptor (6).Although many cell types have the capacity to synthesize and secrete fibronectin, most, if not all, circulating fibronectin is produced by hepatocytes. Hepatocytes in culture secrete fibronectin ...

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“…Hepatokines in turn, such as fibroblast growth factor‐21 and fetuin‐A, regulate AT function and insulin sensitivity. NAFLD, cirrhosis and alcoholic liver also affect pFN levels (Matsuda et al., 1982; Mosher, 1986). Our study suggests that pFN may also act as a hepatokine, and liver‐metabolism mediator.…”

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