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PubMed2001

Vaginal fetal fibronectin levels and spontaneous preterm birth in symptomatic women.

OBJECTIVE: To relate vaginal fetal fibronectin levels in women with symptoms of preterm labor to subsequent spontaneous preterm birth. METHODS: Quantitative fetal fibronectin values were calculated from women who participated in two prospective multicenter trials relating fetal fibronectin to subsequent spontaneous preterm birth. The study populations consisted of women who presented with symptoms of preterm labor between 24(0)/(7) and 34(6)/(7) weeks, a singleton pregnancy, intact membranes, no prior tocolysis, and cervical dilation less than 3 cm. RESULTS: The characteristics of the two study populations were similar. In both populations, the rates of delivery within 7, 14, and 21 days after sampling were clustered into three distinct fetal fibronectin groups (less than 40, 40-100, and 100 ng/mL or more). As fetal fibronectin values increased, the risk of subsequent spontaneous preterm birth also increased. Delivery within 7 days of sampling was 0.4%, 3.3%, and 18.2% (trial A) and 1.4%, 8.0%, 30.0% (trial B) as the fetal fibronectin levels increased from less than 40 ng/mL, to 40-100 ng/mL, and to at least 100 ng/mL, respectively. CONCLUSION: In women with symptoms of preterm labor, an increase in fetal fibronectin from under 40 ng/mL, to 40-100 ng/mL, to at least 100 ng/mL was associated with a progressive increase in the risk of subsequent spontaneous preterm birth. The use of a single fetal fibronectin cutoff of 50 ng/mL for defining a positive test in women with symptoms of preterm labor should be reevaluated.

Adult↗
PubMed2002

Increased plasma fibronectin levels in patients with acute myocardial infarction complicated with left ventricular thrombus.

Fibronectin is a polymorphic and multifunctional glycoprotein that plays a wide-ranging role in hemostasis. In this study, it was aimed to determine plasma fibronectin levels and evaluate its possible role in left ventricular (LV) thrombus formation following acute myocardial infarction (AMI). We have determined clinical, echocardiographic, and biochemical parameters in 97 consecutive patients (aged 59 +/- 13; 87 men/10 women) with first anterior AMI. Two-dimensional echocardiography was performed on Days 1, 3, 7, 15, and 30. Blood samples were obtained within 24-48 h after the onset of symptoms. The study also included 30 healthy control subjects. Plasma fibronectin levels were significantly higher in patients with AMI than control subjects (38 +/- 13 vs. 25.2 +/- 8.7 mg/dl, P=.0001). LV thrombus was detected in 20 (20.6%) of 97 patients. Plasma fibronectin levels were significantly higher in patients with LV thrombus (Group 2) than in patients without LV thrombus (Group 1) (44.5 +/- 11 vs. 36.1 +/-13.4 mg/dl, P=.01). Although univariate analysis showed that plasma fibronectin levels were higher in patients with thrombus, multivariate analysis showed that plasma fibronectin levels were not an independent predictor of LV thrombus formation (P=.059). In multivariate analyses, only peak creatine phosphokinase (CPK) level and LV wall motion score index (WMSI) were independent predictors of thrombus formation (P=.007 and P=.0001, respectively). These results suggest the increased plasma fibronectin levels may be one of the risk factors for LV thrombus formation after AMI. However, further studies concerning the relation between plasma fibronectin levels and LV thrombus formation are necessary.

Adult↗
PubMed1987

Fibronectin in relation to growth patterns of fibrohistiocytic tumours--an immunohistochemical study of benign and malignant fibrous histiocytomas.

Benign and malignant fibrous histiocytomas are composed of an admixture of fibroblast-like and histiocyte-like cells and of a changing amount of fibre structures which tend to be arranged in a so-called storiform pattern. In order to study the organization of the extracellular matrix, the distribution of fibronectin was investigated immunohistochemically. Using the PAP technique and the indirect immunofluorescence method, paraffin sections of formaldehyde fixed tissue specimens of 25 tumours (12 benign fibrous histiocytomas, 12 malignant fibrous histiocytomas, and 1 atypical fibroxanthoma) were studied. A pretreatment with hyaluronidase and proteolytic enzymes (trypsin, pronase, pepsin) was performed to unmask the antigen. Best results were obtained with pronase E or, sometimes even better, by employing a combination of pronase E and hyaluronidase. Generally fibronectin could be demonstrated in the matrix substances of fibrohistiocytic tumours, but the immunohistochemical staining patterns of benign and malignant tumours differed. In benign fibrous histiocytomas, a regular distribution of fibronectin was found in cellular areas. Parallel to formation of collagen fibres, the reaction decreased and in dermatofibromas showing abundant hyalinized collagen the staining proved to be quite weak. In malignant fibrous histiocytomas, the immunostaining was very irregular. In cellular areas consisting of spindle cells, an intense reaction could be observed. Tumours with storiform or fascicular fields exhibit a delicate network of fibronectin encircling individual fibroblast-like cells. In the course of fibre formation, the matrix staining for fibronectin revealed a distribution similar but not identical with that obtained with the reticulin stain. Simultaneous to the occurrence of collagen fibre bundles, fibronectin decreased and in areas of hyalinization the staining was considerably diminished. In areas of undifferentiated small cells, in myxoid zones as well as foci of xanthoma cells, and in pleomorphic portions the immunostain was negative. The distribution in atypical fibroxanthoma is similar to that observed in storiform and pleomorphic variants of malignant fibrous histiocytomas. The results support the suggestion that fibronectin is the first sign of the typical basic pattern of fibrohistiocytic tumours preceding the formation of reticulin and collagen fibres. The expression of fibronectin on cell surfaces as well as in intercellular matrix may be closely related to the organization of the growth patterns of fibrohistiocytic tumours.

Fibronectins↗
PubMed2001

Involvement of calcium signaling in the fibronectin-stimulated macrophage recognition of oxidatively damaged erythrocytes.

Macrophages recognize oxidatively damaged autologous erythrocytes, and cell surface fibronectin of macrophages enhances the recognition (Beppu et al., FEBS Lett. 295 (1991) 135-140). In the present study, mechanisms of enhanced macrophage recognition of oxidatively damaged erythrocytes by fibronectin were investigated. Monolayers of thioglycollate-induced mouse peritoneal macrophages with cell surface fibronectin recognized autologous erythrocytes oxidized with an iron catalyst ADP/Fe(3+). The macrophage recognition of the oxidized erythrocytes was inhibited partially by pretreatment of the macrophage monolayers with a Ca(2+) channel blocker (diltiazem), calmodulin inhibitors (W-7, trifluoperazine, chlorpromazine and dibucaine), an inhibitor of myosin light chain kinase (ML-9), a microfilament formation inhibitor (cytochalasin B), phospholipase A(2) inhibitors (4-bromophenacyl bromide, mepacrine) and cyclooxygenase inhibitors (indomethacin and aspirin). Monolayers of macrophages depleted of fibronectin by trypsinization lost the ability of recognizing oxidized erythrocytes, but acquired the ability when stimulated with a fibronectin-coated coverslip. The recognition of fibronectin-stimulated trypsinized macrophages was also inhibited by the above inhibitors. On treatment with Ca ionophore A23187, trypsinized macrophages acquired the ability to recognize oxidized erythrocytes. The recognition of Ca ionophore-stimulated trypsinized macrophages was inhibited by the above inhibitors except the Ca(2+) channel blocker. These results indicate that the Ca(2+) signaling including Ca(2+) influx, calmodulin activation and myosin light chain phosphorylation are involved in the fibronectin stimulation of the recognition of macrophages for oxidized erythrocytes. Involvement of microfilament formation and arachidonate cascade in the fibronectin stimulation was also suggested.

Animals↗
PubMed1984

Studies on the interaction of human plasma-fibronectin with native type I calf skin collagen molecules using the rotary shadowing technique.

Fibronectin is a ubiquitous glycoprotein found in plasma, on the surface of a number of cell types and in the extracellular matrix. It is believed to function as an adhesive protein for cells by mediating their interaction with connective tissue macromolecules. This study uses the rotary shadowing technique to investigate the interaction between human plasma fibronectin and native calf skin type I collagen molecules. Purified human plasma fibronectin appears fibrillar with a total length of 152 +/- 48 nm (n = 127). Individual molecules of fibronectin interact with one another in an apparent concentration dependent process to form linear polymeric structures up to 10 molecules by end-to-end association. Incubation of various concentrations of fibronectin with collagen results in the interaction of fibronectin with specific sites on the native collagen molecules. In addition, polymeric forms of fibronectin interact with collagen molecules and occasionally bridging structures between collagen molecules are formed. This study provides direct visual demonstration of an interaction between fibronectin and native collagen molecules. Possible physiologic implications of these observations are discussed.

Animals↗
PubMed1991

Serum IgA-fibronectin aggregates in patients with IgA nephropathy and Henoch-Schönlein purpura: diagnostic value and pathogenic implications. The Glomerular Disease Collaborative Network.

IgA nephropathy is a common form of glomerulonephritis that has varied clinical expressions, ranging from asymptomatic hematuria to rapidly progressive nephritis. We report the strong association (P less than 0.0001) of circulating IgA-fibronectin aggregates with IgA nephropathy. Of 30 patients with IgA nephropathy, 93.3% had serum IgA-fibronectin aggregates detected with an enzyme immunoassay using collagen as a substrate to bind the aggregates. Among the patients with IgA-fibronectin aggregates were patients with Henoch-Schönlein purpura and recurrent crescentic IgA nephropathy in transplants. Only 11.7% of 103 patients with other types of glomerular disease and 6.7% of normal controls had positive IgA-fibronectin aggregate assay levels. IgA-fibronectin aggregates also were detected in serum using an antifibronectin antibody capture assay; and could be depleted from serum by heparin-agarose affinity chromatography. The circulating IgA-fibronectin aggregates had the same unusual predominance of lambda relative to kappa light chains that is observed in the glomerular deposits of IgA nephropathy. The data indicate that IgA-fibronectin aggregates are a useful serologic marker for IgA nephropathy, Henoch-Schönlein purpura, and recurrent IgA nephropathy in transplants. The presence of fibronectin in the circulating aggregates may play an important role in the preferential deposition of nephritogenic IgA-containing immune complexes in the mesangium of patients with IgA nephropathy.

Antigen-Antibody Complex↗
PubMed1996

Serologic study of immunoglobulin A-fibronectin aggregates in immunoglobulin A nephropathy.

The immunoglobulin A (IgA)-fibronectin aggregates, detected by enzyme-linked immunosorbent assay using either antifibronectin or collagen I as binding protein, were previously found to be raised in the circulation of patients with IgA nephropathy (IgAN). It has been suggested that IgA-fibronectin aggregates are involved in the pathogenesis and that the plasma IgA-fibronectin level may even be of diagnostic value in IgAN. Nevertheless, a recent report has questioned the specificity of these assays as plasma IgA may interact with immobilized IgG and these assays detect not only IgA-fibronectin, but also total plasma IgA. These doubts render the interpretation of raised IgA-fibronectin aggregates in IgAN impossible. We isolated total IgA, in plasma by jacalin-agarose. Monomeric and polymeric IgA1 were distinctly separated by fast protein liquid chromatography. When the fast protein liquid chromatography fractions were analyzed for IgA-fibronectin using the antifibronectin capture assay, increased optical density values were predominantly observed in polymeric IgA but not in monomeric IgA. Similar findings were found when the fast protein liquid chromatography fractions were studied using a novel gelatin-anti-IgA assay that avoided nonspecific interaction between plasma IgA and immobilized IgG used as the capture antibody in antifibronectin capture assay. Using our gelatin-anti-IgA assay, we failed to demonstrate a diagnostic increase in IgA-fibronectin aggregates in polymeric IgA from patients with IgAN compared with controls. Our finding of circulating IgA-fibronectin aggregates in patients with IgAN comparable to those of healthy controls did not support the notion that these aggregates may have a pathogenetic role or diagnostic value in IgAN.

Antibodies↗
PubMed1983

[Purification of human fibronectin by precipitation and immunoadsorption].

Two types of human plasma fibronectin concentrate were obtained by simple, large scale, precipitation methods. Concentrate 1 contains 90% pure fibronectin in a mainly dimeric form. This easy, high yield method provides a functional fibronectin suitable for intravenous therapeutic purposes in deficient patients. Concentrate 2 contains 95-98% pure fibronectin with minimal amounts of fibronectin monomer and degradation products. It seems well adapted to serum free cultures of human cells. A third preparation of an apparently pure fibronectin has also been obtained by immuno-adsorption with a Sepharose 4B column to which has been coupled an anti-fibronectin monoclonal antibody. The capture of dimer, monomers and degradation products by this antibody and their release at pH 2.4 has been demonstrated by gel transfer on nitrocellulose sheet revealed by another monoclonal anti-fibronectin antibody labelled with peroxidase.

Animals↗
PubMed1998

Fibronectin-binding activity in Borrelia burgdorferi1.

Recently, the term MSCRAMM (microbial surface components recognizing adhesive matrix molecules), has been introduced to describe microbial molecules that recognize extracellular matrix (ECM) [1]. Here we present evidence for the presence of fibronectin-binding molecules in Borrelia burgdorferi and several other Borrelia species. Immunofluorescence studies show that plasma fibronectin is bound uniformly over the cell surface of free swimming B. burgdorferi. In addition, the spirochetes are able to bind to plasma fibronectin-coated microwell plates, an interaction that is inhibited by anti-fibronectin antibody as well as exogenous plasma fibronectin. Taken together, the data suggest that fibronectin binds to the surface of the spirochete. On Western blot-like assays, B. burgdorferi and some B. afzelii strains express a major fibronectin-binding protein (Fn-BA) with an approximate molecular mass of 52 kDa. In addition, several other major Fn-BAs were found in B. hermsii (26, 31, 33, 39, 46, 54 and 58 kDa) and B. turicatae (39, 41, 45, 50, 56, 59 and 66 kDa). Preliminary evidence suggests that fibronectin (and Fn-BA) may play a role as a molecular bridge between the spirochete and other components of the extracellular matrix.

Adhesins, Bacterial↗
PubMed1990

Fibronectin-staphylococcal interactions in endovascular infections.

Fibronectin is a large molecular weight protein that is found coating the surfaces of sites where endovascular damage has occurred. These are also the sites most commonly infected by bacteremic strains of staphylococci. Epidemiologic studies show a correlation between expression of fibronectin receptors and development of invasive infections. In vitro studies using cultured cells, artificial matrices containing fibronectin, blood clots, natural inflammatory matrices, and anti-fibronectin antibodies implicate fibronectin as an important ligand for staphylococcal attachment to host tissues and prosthetic devices. In the rat endocarditis model, S. aureus strains that lack the fibronectin receptor due to site-directed mutagenesis were unable to colonize the traumatized heart valves. These data suggest that the fibronectin receptor on staphylococci is important in the pathogenesis of endovascular infections. Because the fibronectin receptor is widely expressed on pathogenic of staphylococci, a broadly protective vaccine against S. aureus might be possible.

Animals↗
PubMed1997

Altered collagen of human pathological fibroblasts impairs the synthesis of fibronectin.

Human fibroblasts with mutated type I collagen have marked defective adhesive capacities on exogenous type I collagen and exogenous fibronectin in comparison to normal fibroblasts. This defective cell adhesion could be partly explained by the decreased level of cell surface receptors of the beta 1-integrin family, i.e., the alpha 2 integrin subunit for type I collagen and the alpha 5 integrin subunit for fibronectin, observed in pathological fibroblasts. However, it appeared that the presence of altered collagen interfered both with fibronectin biosynthesis and with its surface expression. Using a binding assay on immobilized fibronectin, we demonstrated that the mutated collagen had a weaker binding to fibronectin. In addition, the pathological fibroblasts plated on a mixture of normal exogenous type I collagen and fibronectin exhibited the same maximal level of adhesion as control fibroblasts. These results indicate that fibroblasts with the mutated collagen exhibit a decreased binding to normal fibronectin, a modification of synthesis and surface expression of fibronectin, and, finally, altered adhesive capacities.

Cell Adhesion↗
PubMed1988

A calorimetric analysis of human plasma fibronectin: effects of heparin binding on domain structure.

Fibronectin domain structure, as influenced by interaction with heparin, calcium, or chondroitin sulfate C, was analyzed by differential scanning calorimetry. A complex thermal denaturation transition was observed with a large sharp endotherm at 63 degrees C, a broad endotherm between 70 and 80 degrees C, and an exotherm at 80-90 degrees C. Analysis of the denaturation profiles revealed the existence of four thermal transitions, 59.1, 62.2, 67.3, and 74.3 degrees C, and an exotherm at 83.9 degrees C. The calorimetric enthalpies of the four endotherms are 1146 +/- 259, 866 +/- 175, 1010 +/- 361, and 676 +/- 200 kcal/mol, respectively. In all cases, the calorimetric to van't Hoff enthalpy ratio was greater than 1.0. Computer analysis of the primary structure of fibronectin revealed 29 +/- 8% homology among the type I homology units and 28 +/- 7% homology among type III homology units, suggesting that different structural domains could arise from the same homology type. This may explain why more thermal transitions are observed for fibronectin than there are homology types. Addition of heparin to fibronectin in varying molar ratios, i.e., 10:1 to 30:1, resulted in a larger calorimetric enthalpy for the first type of structural domain (Tm = 59.1 degrees C) of fibronectin. At higher heparin to fibronectin ratios (40:1 or 75:1), the enthalpy of this domain decreased, while the others remained unchanged. In the presence of 5 mM calcium chloride, fibronectin thermal denaturation occurred at lower temperatures and was associated with precipitation of fibronectin.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed2000

Imaging and mapping heparin-binding sites on single fibronectin molecules with atomic force microscopy.

Fibronectin is composed of multiple homologous repeats and contains many functional domains. Two major heparin-binding domains have previously been identified: the Hep I site near the amino terminus and the Hep II site near the carboxyl terminus. The Hep II site has been considered the high-affinity heparin-binding site based on studies of fibronectin fragments. However, few studies have been carried out on heparin binding by intact fibronectin. We imaged single fibronectin molecules as well as heparin-coated gold particles bound to whole dimeric plasma fibronectin molecules with tapping mode atomic force microscopy. We observed heparin-gold particles preferentially bound at two locations that correspond to the Hep I and Hep II sites. Quantitative analysis of images of individual fibronectin-heparin-gold complexes showed that almost twice as many heparin-gold particles bound to the N-terminal Hep I site compared to the Hep II site. In contrast to previous findings with fibronectin fragments, these results suggest that the Hep I site has a binding affinity higher than or comparable to the Hep II site in the intact fibronectin molecule.

Animals↗
PubMed1997

Influence of surface treatments developed for oral implants on the physical and biological properties of titanium. (II) Adsorption isotherms and biological activity of immobilized fibronectin.

The influence of titanium surface properties on in vitro adsorption isotherms of fibronectin, promotion of Staphylococcus aureus adhesion, and binding of a monoclonal antibody to the cell-binding domain of fibronectin was examined. Treatments producing different surface roughness were applied to a single side of commercially pure titanium coverslips, which was either mechanically polished (P), or polished and then acid attacked with H2SO4/HCl (PA), or sandblasted and then acid attacked (SLA), whereas the untreated side was blocked by an albumin coating layer. Incubation of the coverslips with concentrations of soluble 3H-labelled fibronectin increasing from 1 to 16 micrograms/ml led to the saturation of all surfaces with immobilized protein from 4 to 16 micrograms/ml. Promotion of S. aureus adhesion by fibronectin adsorbed on all surfaces and binding of the monoclonal antibody to its cell-binding domain was to some extent proportional to the amount of immobilized protein but also showed some minor differences between surfaces. More important material-related differences were observed when fibronectin adsorption isotherms were expressed as a function of the effective, roughness-corrected surface area, yielding amounts of immobilized fibronectin on the rough PA and SLA titanium surfaces which were 50% lower than those adsorbed on either smooth P or polymethylmethacrylate coverslips used as controls. In conclusion, surface treatments increasing the surface roughness of titanium do not increase, but may partly decrease in vitro adsorption of fibronectin. Despite adsorbing different amounts of fibronectin, both rough and smooth titanium surfaces promote normal expression of 2 major functional domains of this protein.

Adsorption↗
PubMed2001

Serum-free cultured keratinocytes fail to organize fibronectin matrix and possess different distribution of beta-1 integrins.

The development of serum free medium formulation for culturing keratinocytes was a breakthrough in achieving a high number of epidermal cells for experimental and therapeutic studies, in particular to support the wound healing process. It is not clear, however, if switching the cells to highly proliferative phenotype may reflect change in other cellular functions important for the wound repair as their adhesive interactions with the extracellular matrix components. Remodelling of the extracellular matrix, particularly of fibronectin plays an essential role for guiding the cells during wound healing. The molecular mechanisms for organization of this provisional fibronectin matrix, however, are still not clear. We found that keratinocytes in serum containing medium, although in fewer numbers than fibroblasts, were able to remove adsorbed fluorescent labelled fibronectin from the substratum and reorganize it in a fibrilar pattern along the cell periphery. After 3 days the secreted fibronectin had also been organized as matrix-like fibers and as clusters deposited on the substratum after migrating cells. In contrast, serum free cultured keratinocytes fail to organize pre-adsorbed fluorescent labelled fibronectin, as well as the secreted fibronectin, although they grow very well under these conditions. Switching the cells to serum containing medium initiates the removal of fluorescent labelled fibronectin from the substratum, however without reorganization in fibrillar pattern. Most likely, these keratinocytes remove fluorescent labelled fibronectin by the expression of proteolytic activity, rather than with the mechanical function of beta(1) integrins. The latter were diffusely dispersed in serum containing conditions and tend to organize in focal adhesions in serum free cultured cells. We assumed their transient expression and different affinity state might be important for the keratinocyte migration and matrix assembly mechanism.

Blood Physiological Phenomena↗
PubMed1993

The extracellular matrix of reparative tissue in the vitreous: fibronectin production in proliferative diabetic retinopathy membranes.

In a preliminary investigation into the origins of the extracellular matrix glycoprotein fibronectin in proliferative diabetic retinopathy (PDR) membranes, four globes containing PDR membranes were subjected to in situ hybridisation and immunohistochemical studies. Fibronectin mRNA was found in PDR membrane cells in two of the four globes. The fibronectin-producing cells exhibited fibroblast-like or macrophage-like morphology. Occasional intraretinal macrophage-like cells which contained fibronectin mRNA were also observed in three of the eyes. Variable fibronectin immunoreactivity was observed in all the PDR membranes, while the fibronectin staining pattern in the underlying retina was similar to that reported for albumin in eyes with breakdown of the blood-retina barrier. The findings suggest that fibronectin in PDR membranes originates from both plasma-derived fibronectin and the membrane cells, and support the concept that extracellular matrix components play an important role in PDR membrane progression.

Aged↗
PubMed2003

Fibronectin requirement in branching morphogenesis.

Many organs, including salivary glands, lung and kidney, are formed during embryonic development by epithelial branching. In branching morphogenesis, repetitive epithelial cleft and bud formation create the complex three-dimensional branching structures characteristic of many organs. Although the mechanisms are poorly understood, one might involve the site-specific accumulation of some regulatory protein. Here we show that the extracellular matrix protein fibronectin is essential for cleft formation during the initiation of epithelial branching. Fibronectin messenger RNA and fibrils appeared transiently and focally in forming cleft regions of submandibular salivary-gland epithelia, accompanied by an adjacent loss of cadherin localization. Decreasing the fibronectin concentration by using small interfering RNA and inhibition by anti-fibronectin or anti-integrin antibodies blocked cleft formation and branching. Exogenous fibronectin accelerated cleft formation and branching. Similar effects of fibronectin suppression and augmentation were observed in developing lung and kidney. Mechanistic studies revealed that fibrillar fibronectin can induce cell-matrix adhesions on cultured human salivary epithelial cells with a local loss of cadherins at cell-cell junctions. Thus, fibronectin expression is required for cleft formation in branching morphogenesis associated with the conversion of cell-cell adhesions to cell-matrix adhesions.

Animals↗
PubMed2006

Modulation of cell-fibronectin matrix interactions during tissue repair.

Environmental signals from the extracellular matrix (ECM) are transmitted by cell surface receptors that connect to the actin cytoskeleton and to multiple intracellular signaling pathways. To dissect how the ECM regulates cell functions, we are using a three-dimensional (3D) fibrin-fibronectin matrix, resembling the wound provisional matrix. Fibroblasts adhere to fibronectin in this matrix via concomitant engagement of alpha 5 beta 1 integrin receptors and syndecan-4, a transmembrane proteoglycan. An adhesive phenotype is developed with actin stress fibers and activation of focal adhesion kinase (FAK) and Rho GTPase. Lack of syndecan-4 engagement, as occurs in the presence of the ECM protein tenascin-C, promotes a motile phenotype; FAK and Rho signaling are downregulated and filopodia are extended. Fibronectin matrices have distinct effects on two other receptors: alpha 4 beta 1 and beta v beta 3 integrins. Although alpha 4 beta 1 does not naturally support strong cell interactions with a fibrin-fibronectin matrix, binding is dramatically enhanced by proteolytic cleavage of fibronectin. Conversely, activity of alpha v beta 3 is stimulated by multimeric fibronectin fibrils showing that the organization of fibronectin differentially affects integrin functions. Thus, deposition of additional ECM components, expression of co-receptors for ECM, cleavage of adhesive proteins, and the architecture of the ECM microenvironment are different mechanisms for modulating cell responses to fibronectin matrix.

Animals↗