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PubMed1994

Stimulation of fibronectin production and deposition by chicken granulosa cells in vitro by epidermal growth factor and transforming growth factor alpha.

Experiments were conducted in vitro to examine the effect of epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha) on the production of fibronectin (deposited, secreted into medium and cell-associated) by hen granulosa cells isolated from the largest (F1; about 35 mm in diameter, mature) and third largest (F3; 15-20 mm in diameter) preovulatory follicles, as well as from a pool of immature small yellow follicles (6-8 mm in diameter). The cells were incubated in culture wells coated with type IV collagen or in wells without collagen coating, and the amounts of fibronectin produced were measured using a specific ELISA. The total amount of fibronectin produced by unstimulated cells was greatest in wells containing F1 cells and increased with time. The amount of fibronectin deposited by unstimulated cells was greatest in wells containing F1 cells and was much higher in collagen-coated wells than in uncoated wells. Both EGF and TGF-alpha increased the quantity of fibronectin deposited by granulosa cells in collagen-coated and uncoated wells. Fibronectin secreted into the medium by unstimulated cells also increased with the stage of follicular maturation and was enhanced by EGF and TGF-alpha. The quantity of cell-associated fibronectin in granulosa cells in collagen-coated and uncoated wells was also increased by these growth factors. Type IV collagen did not have any appreciable effect on the amount of fibronectin present in the incubation medium or on cell-associated fibronectin. Because of its marked effect on deposited fibronectin, there were greater total quantities of fibronectin in culture wells coated with type IV collagen. These results demonstrate that EGF and TGF-alpha stimulate the production and deposition of fibronectin by chicken granulosa cells. The results also suggest that in combination with collagen IV, these growth factors can regulate the formation of the extracellular matrix (for example, basal lamina) of the hen ovarian follicle.

Animals↗
PubMed1999

Fibronectin induces pseudopod formation and cell migration by mobilizing internal Ca(2+) in blastoderm cells from medaka embryos.

During vertebrate embryogenesis, blastoderm cells at the gastrula stage migrate to new locations for subsequent development. The cellular mechanism of migration was studied in medaka (Oryzias latipes) embryos at the early gastrula stage. When fibronectin was applied iontophoretically or by the puff method, cell surface protrusion known as pseudopods and a local [Ca(2+)](i) rise at the site of application were observed in approximately half of the isolated blastoderm cells. When the pseudopod adhered to the substrate, the cell body moved toward the direction of the pseudopod as [Ca(2+)](i) declined and the pseudopod was withdrawn. Local puff application of ionomycin, a Ca(2+) ionophore, in the presence of external Ca(2+) induced protrusions of the plasma membrane similar to pseudopods, suggesting that the [Ca(2+)](i) rise itself is causing pseudopod formation. On the other hand, fibronectin induced pseudopods even in the absence of external Ca(2+), suggesting the mobilization of Ca(2+) from internal stores. In accordance with this interpretation, fibronectin failed to induce [Ca(2+)](i) rises after pretreatment with thapsigargin, a blocker of Ca(2+)-ATPase in the endoplasmic reticulum. Furthermore, chelating internal Ca(2+) with BAPTA prevented fibronectin from inducing pseudopods. U-73122, a blocker of phospholipase C, completely suppressed both the [Ca(2+)](i) rise and morphological changes accompanied with fibronectin application, suggesting involvement of the inositol phosphate pathway. On the other hand, caffeine evoked a [Ca(2+)](i) rise in a great majority of the fibronectin-responsive cells and the percentage of fibronectin-responsive cells was greatly reduced by a blocking dose of ryanodine. These results suggest that fibronectin activates phospholipase C and the initial [Ca(2+)](i) rise through IP(3) receptors further activates ryanodine receptors, achieving the local [Ca(2+)](i) rise. The decay time course of [Ca(2+)](i) after fibronectin application was prolonged in the absence of external Na(+). DCB, an inhibitor of Na(+)/Ca(2+) exchangers, also prolonged the time course of the [Ca(2+)](i) decay, suggesting the contribution of Na(+)/Ca(2+) exchangers. Cytochalasin D, an inhibitor of actin polymerization by binding to the barbed end of F-actin, induced swelling in fibronectin-responsive cells and prevented fibronectin from inducing pseudopod formation without suppressing the [Ca(2+)](i) rise. These results support the hypothesis that fibronectin facilitates cell migration via pseudopod formation during gastrulation.

Animals↗
PubMed1993

Follicle-stimulating hormone-enhanced fibronectin production by chicken granulosa cells is influenced by follicular development.

Experiments were conducted in vitro to examine the effect of ovine follicle-stimulating hormone (FSH) on various fractions of fibronectin (deposited, secreted in medium, and cell-associated) resulting from culture (12 or 24 h) of chicken granulosa cells isolated from the largest (F1) and third largest (F3) preovulatory follicles as well as from a pool of immature small yellow follicles (SYF). Fibronectin in each fraction was quantified with a specific ELISA. The amount of fibronectin deposited in culture wells containing unstimulated cells increased with time and was greatest in wells containing F1 cells. Follicle-stimulating hormone increased the quantity of fibronectin deposited within 12 h by F3 and SYF cells, but not by F1 cells. The magnitude of FSH-enhanced fibronectin deposition was greatest in cells derived from immature SYF. Fibronectin secreted in the medium by unstimulated cells also increased with the stage of follicular maturation. Follicle-stimulating hormone increased the amount of fibronectin secreted in the medium by F3 and SYF cells. The quantity of fibronectin associated with cells was increased by FSH in all cell types. Total (deposited plus medium plus cell-associated) fibronectin production was elevated in a dose- and time-dependent manner when FSH was added to F3 and SYF granulosa cells, but the gonadotropin was without effect in F1 cells. The magnitude of FSH stimulation (fold increase) of total fibronectin production was calculated as a multiple of the unstimulated (control) value for each cell type. The relative change in total fibronectin production resulting from addition of FSH (after 24 h incubation) was .02- to .24-fold in F1 cells as compared with .33- to .92-fold in F3 cells and 2.75- to 4.38-fold in SYF cells. These results indicate that FSH stimulates fibronectin production by chicken granulosa cells, and this stimulatory effect decreases as the follicle matures.

Animals↗
PubMed1983

Fibronectin in cultured rat keratinocytes: distribution, synthesis, and relationship to cytoskeletal proteins.

The aim of this study was to investigate whether epidermal cells can synthesise fibronectin and whether the distribution of this glycoprotein is related to the adhesion and cytoskeletal organisation of these cells. The production of fibronectin by newborn rat epidermal cells was shown by indirect immunofluorescence staining of cultures grown in the absence of a feeder layer using an antiserum which had been cross-adsorbed with foetal calf serum proteins to remove antibodies which recognised serum fibronectin. The distribution of fibronectin in areas of cell-cell and cell-substratum contact, characteristically in the form of short radial stitches, was examined in more detail using immunoelectron microscopy with colloidal gold as marker. This showed the close proximity of fibronectin to the cell membrane, with the ventral surface and fine cellular processes showing the heaviest labelling, and also revealed evidence of a relationship between external fibronectin and internal structure in epidermal cells. Immunofluorescence showed that tonofilaments (keratin) and microtubules were present as fibrillar arrays but were not related to fibronectin distribution. Vimentin and desmin were absent. Actin was distributed as a circumferential bundle of filaments, with finer stands running radially to the edge. The latter were reminiscent of the radial fibronectin stitches and a spatial correspondence between fibronectin and actin was confirmed by double-label immunofluorescence which revealed many instances of overlap and colinearity of actin and fibronectin filaments. The ability of keratinocytes to produce fibronectin suggests that these cells can contribute to the formation of the basement membrane in skin. The localisation of fibronectin and its close association with actin also suggests that it is involved in keratinocyte adhesion and is related to the internal organisation of these cells.

Actins↗
PubMed1991

Fibronectin dependent macrophage fibrin binding.

Plasma fibronectin has been shown to increase the binding of fibrin monomer to macrophages in vitro. In the present study we began characterization of the mechanism underlying this fibronectin activity. Fragments of fibronectin containing the amino terminus enhanced macrophage fibrin binding to the same extent as intact fibronectin on an equimolar basis. However, fibronectin fragments containing the gelatin-binding domain or the cell-binding domain, but lacking the amino terminus, had no effect on fibrin binding. Fibronectin enhanced fibrin binding was not affected by the addition of synthetic peptides containing the RGD adhesion sequence. The ability of fibronectin to augment fibrin binding remained after paraformaldehyde fixation of macrophage monolayers. Fixation did not alter the basal levels of fibrin binding by macrophages. Preincubation of macrophages with exogenous fibronectin did not increase the binding of fibrin. Fibronectin enhanced fibrin binding remained unaltered after the removal of endogenous cell surface fibronectin by capping with F(ab')2 fragments of antibodies to fibronectin. These results suggest that the amino terminus of fibronectin supports the attachment of fibrin to macrophages by an initial fluid-phase interaction that precedes cellular binding and does not require a cellular response.

Amino Acid Sequence↗
PubMed1989

Effect of fibronectin on C3b and Fc receptor-mediated phagocytosis by peripheral blood monocytes in uraemic patients.

The influence of human fibronectin was evaluated on the phagocytosis in vitro of C. albicans (C3b receptor-mediated) and IgG antibody-coated sheep erythrocytes (Fc receptor-mediated) by the peripheral blood monocytes of 40 uraemic patients undergoing periodic haemodialysis. Some nutritional parameters (albumin, transferrin, C4, C3, haematocrit, lymphocyte count, height and bodyweight) were also evaluated. Results showed significantly decreased plasma fibronectin (P less than 0.001) and reduced C3b receptor (R)- and FcR-mediated phagocytosis in uraemic patients (P less than 0.001). A strict correlation was found between fibronectin and C3bR-mediated phagocytosis (P less than 0.001) and between fibronectin and FcR-mediated phagocytosis (P less than 0.05). In 20 patients with decreased fibronectin concentrations and reduced phagocytic function, the in vitro incubation of peripheral blood monocytes with 50 micrograms/ml of purified fibronectin significantly enhanced C3bR-(P less than 0.001) but not FcR-mediated phagocytosis. Study of nutritional parameters in the uraemic patients revealed that values of fibronectin, C3, IgG and albumin were significantly reduced. Fibronectin correlated significantly (P less than 0.001) with C3. A good relationship (P less than 0.05) was also found between the plasma fibronectin and bodyweight loss. A greater incidence of infectious disease was observed in patients with decreased plasma fibronectin than in uraemic patients with normal values (P less than 0.05). The results suggest that a decrease in plasma fibronectin in uraemic patients could impair the peripheral blood monocyte phagocytic capacity and be potentially dangerous, predisposing the patient to infections. The determination of fibronectin concentration in these patients may, therefore, have a potential value as an indicator of peripheral blood monocyte phagocytic function.

Adult↗
PubMed1988

Factor XIII cross-linking of fibronectin at cellular matrix assembly sites.

We describe the effect of activated Factor XIII (Factor XIIIa, plasma transglutaminase) on the incorporation of plasma fibronectin into extracellular matrix by cultured human fibroblasts. In the absence of added Factor XIIIa, fibronectin binds to cultured fibroblast cell layers and is assembled into disulfide-bonded multimers of the extracellular matrix. When Factor XIIIa was included in the binding medium of skin fibroblasts, accumulation of 125I-fibronectin in the deoxycholate-insoluble matrix was increased. Fibronectin accumulating in the cell layer was cross-linked into nonreducible high molecular weight aggregates. The 70-kDa amino-terminal fragment of fibronectin inhibited the binding and cross-linking of 125I-fibronectin to cell layers, whereas fibrinogen had little effect. When 125I-fibronectin was incubated with isolated matrices or with cell layers pretreated with cytochalasin B, it did not bind and could not be cross-linked by Factor XIIIa into the matrix. HT-1080 human fibrosarcoma cells bound exogenous fibronectin following treatment with dexamethasone; Factor XIIIa cross-linked the bound fibronectin and caused its efficient transfer to the deoxycholate-insoluble matrix. These results indicate that exogenous fibronectin is susceptible to Factor XIIIa-catalyzed cross-linking at cellular sites of matrix assembly. Thus, Factor XIIIa-mediated fibronectin cross-linking complements disulfide-bonded multimer formation in the stabilization of assembling fibronectin molecules and thus enhances the formation of extracellular matrix.

Cell Line↗
PubMed1986

Comparative effect of circulating bacterial or nonbacterial particulates on plasma fibronectin: relationship to lung deposition of blood-borne foreign particles.

Reticuloendothelial (RE) phagocytic function and plasma fibronectin are altered early after trauma and during septic shock. Since fibronectin-coated particles will tend to aggregate if not efficiently phagocytized, we hypothesized that elevated fibronectin levels during hepatic and/or splenic RE depression could potentiate the lung deposition of blood-borne foreign microparticles. To evaluate this concept, we measured plasma fibronectin, hepatic RE function, and tissue deposition of blood-borne colloids in rats after they were injected with nonbacterial and bacterial particulates. Rats were injected intravenously with gelatin-coated colloids (50 mg/100 gm) to simulate blood-borne collagenous tissue debris after trauma, or with live Pseudomonas aeruginosa (1 X 10(9)/rat) to simulate bacterial entrance into the blood with sepsis, or with both to simulate sepsis after trauma. Phagocytic function was evaluated by liver and spleen uptake of gelatinized 125I RE test emulsion. Fibronectin was quantified by electroimmunoassay. There was an acute 60-80% decrease in plasma fibronectin 2 hr following either colloid or colloid coupled with bacterial infusion. Bacterial infusion alone elicited only a mild 20% decrease in fibronectin by 2 hr. By 24 hr, restoration of fibronectin levels was observed in all groups with hyperfibronectinemia observed in animals challenged with Pseudomonas. Following colloid alone, liver uptake of the RE test particle was acutely depressed at 2 hr in association with an acute depletion of fibronectin, but at 24 hr the RE depression persisted even with normalization of fibronectin. In contrast, with only bacteremia, the rebound elevation of fibronectin was associated with increased hepatic RE function. In rats given both colloid and Pseudomonas, the hyperfibronectinemia (60-100% above controls) at 24 hr coexisted with inadequate liver phagocytic uptake ability. This resulted in a significant 20-fold (P less than 0.05) increment in lung localization of the blood-borne test microparticles. Thus, hyperfibronectinemia without a parallel increase in liver phagocytic ingestive ability may actually enhance lung localization of blood-borne microparticles, which have a high affinity for fibronectin.

Animals↗
PubMed1985

Structure of the carbohydrate units of human amniotic fluid fibronectin.

Human amniotic fluid fibronectin was found to contain three types of carbohydrates: complex-type N-glycosidic glycans, lactosaminoglycans, and O-glycosidic glycans. The structures of the complex-type glycans were established by carbohydrate and methylation analysis, Smith degradation, sequential exoglycosidase treatments, lectin chromatography, and DEAE-Sephadex chromatography. Lactosaminoglycans were analyzed by fast atom bombardment mass spectrometry, and the O-glycosidically-linked oligosaccharides by gas-liquid chromatography-mass spectrometry and high-pressure liquid chromatography. The results show that amniotic fluid fibronectin contains 2 mol of biantennary and 2-3 mol of triantennary, complex-type N-glycosidic glycans. Unlike the N-glycosidic glycans of human adult plasma fibronectin, which contain only traces of fucose and are completely sialylated, the glycans from amniotic fluid fibronectin are fucosylated and only partially sialylated. The complex-type N-glycosidic glycans present in amniotic fluid fibronectin also include a fractional amount (0.1 mol) of glycans with a polylactosaminyl structure. In addition, 4 mol of O-glycosidic oligosaccharides, which have not previously been described in fibronectins, were found in amniotic fluid fibronectin. The major oligosaccharides in this fraction have the structures Gal beta 1----3GalNAcol, NeuNAc alpha 2----3Gal beta 1----3GalNAcol and NeuNAc alpha 2----3Gal beta 1----3(NeuNAc alpha 2----6)GalNAcol. O-glycosidically linked oligosaccharides were also detected in human adult plasma fibronectin but in smaller amounts than in amniotic fluid fibronectin. These results show that amniotic fluid fibronectin differs from plasma fibronectin with regard to the number of glycans attached to the polypeptide and that the glycans present in these two fibronectins differ in structure.

Amniotic Fluid↗
PubMed1985

Heparin binding is necessary, but not sufficient, for fibronectin aggregation. A fluorescence polarization study.

Analysis of parameters governing heparin binding to fibronectin indicates that heparin binding is a necessary, but insufficient, condition for fibronectin cryoprecipitation. Heparin binding to fibronectin is a rapid, readily reversible event which can occur under several conditions which prohibit fibronectin cryoprecipitation. While cryoprecipitation of fibronectin is abolished at temperatures in excess of 10 degrees C, appreciable heparin binding to fibronectin does occur even at 40 degrees C. While increasing ionic strength and pH inhibit both heparin binding and cryoprecipitation of fibronectin, heparin binding can still occur at high ionic strengths and pH values which completely abolish cryoprecipitation. Scatchard analysis of fluorescent polarization data reveals a biphasic heparin binding curve with high and low affinity Kd values of 3.5 X 10(-8) and 10(-6) M, respectively. In contrast to heparin binding, fibronectin aggregation is a cooperative phenomenon. Fibronectin cryoprecipitation is greatly reduced at temperatures above 10 degrees C, at pH values above pH 10, and at ionic strengths above 0.3 M. Thus, heparin binding and protein aggregation are separate events which occur during fibronectin cryoprecipitation. Results obtained here via fluorescence polarization in conjunction with other physical measurements suggest that a decrease in flexibility of the fibronectin molecule is associated with the protein aggregation step of cryoprecipitation. The role of heparin in the mechanism of fibronectin cryoprecipitation is discussed.

Animals↗
PubMed1983

Characterization of the fibronectin synthesized by human germ cell tumors.

The ability of the human germ cell tumor cell lines Tera 1, Tera 2, PA-1, LICR LON HT 39/7, LICR LON HT3B1, and LICR LON HT 53 to synthesize and secrete fibronectin has been studied. The presence of cellular fibronectin was examined using indirect immunofluorescence, whereas the synthesis and secretion of the protein were studied using specific immunoprecipitation from cultures radioactively labeled with [35S]methionine. Two of the cell lines, LICR LON HT 39/7 and Tera 1, did not synthesize fibronectin, whereas all the other cell lines did. Plasma membrane fibronectin could not be demonstrated on any of the cell lines, although cytoplasmic fibronectin was easily demonstrable. The cells appear therefore to synthesize fibronectin but not retain it. Sodium dodecyl sulfate:polyacrylamide gel electrophoresis of the secreted fibronectin produced by the human teratoma cell lines showed that it had an apparent molecular weight greater than that produced by adult human breast fibroblasts or human plasma fibronectin. Peptide mapping of this secreted germ cell tumor fibronectin, by partial proteolytic cleavage, yielded peptide patterns similar to those obtained from either human plasma fibronectin or adult human breast fibroblast fibronectin. The difference in molecular weight between the fibronectins may therefore be due to changes in their patterns of glycosylation.

Cell Line↗
PubMed1983

Opsonic fibronectin deficiency in patients with intra-abdominal infection.

The reticuloendothelial system provides host defense functions by the intravascular phagocytosis of bacteria and nonbacterial particulates. Fibronectin is opsonic for reticuloendothelial phagocytosis. Plasma fibronectin was measured before and after operation in patients with intra-abdominal infection. Preoperatively opsonic fibronectin was reduced by 39% of normal control levels in 16 patients with intra-abdominal infection. There was an even greater reduction of opsonic fibronectin after operation that was first observed in the recovery room. This deficiency persisted for the first 4 days with a tendency toward recovery of normal circulating levels by the fifth postoperative day. In contrast, patients who underwent elective major abdominal operation without infection manifested a transient opsonic fibronectin deficiency with recovery by the second and third postoperative days. Eight of 16 patients with intra-abdominal infection developed multiple organ failure. The opsonic fibronectin levels in those patients were lower than the levels in eight patients who did not develop multiple organ failure. Furthermore, there was no tendency toward recovery of normal circulating opsonic fibronectin in those patients. On all days when multiple organ failure occurred there was a marked deficiency of circulating opsonic fibronectin. We conclude that transient opsonic fibronectin deficiency occurs after major elective abdominal operation. Patients with intra-abdominal infection manifest opsonic fibronectin deficiency before operation, and further depletion of opsonic fibronectin occurs after operation. Postoperative multiple organ failure occurs only in association with severe opsonic fibronectin deficiency.

Abdomen↗
PubMed1993

Alternatively spliced fibronectin molecules in the wounded cornea: analysis by PCR.

PURPOSE: To determine whether certain fibronectin isoforms participate in corneal epithelial wound healing, the authors used the polymerase chain reaction to detect different splicing patterns of the EIIIA segment of fibronectin mRNA in epithelial scrape-wounded cornea of rats. METHODS: Specific fibronectin cDNA sequences synthesized from rat cornea with total RNA were amplified with various sets of synthetic oligonucleotide primers. RESULTS: The authors detected both the EIIIA+ and EIIIA- fibronectin mRNA isoforms during corneal wound healing. The kinetics of corneal expression of both total fibronectin mRNA and the EIIIA- fibronectin mRNA isoform was polyphasic; an initial decrease was followed by an increase at 45 minutes, a second increase at 2 hours, and a third increase at 4 days after wounding. EIIIA+ fibronectin mRNA, not found in normal cornea, also was detected during healing. CONCLUSIONS: The expression of total fibronectin mRNA and both the EIIIA+ and EIIIA- fibronectin mRNA is upregulated during corneal epithelial wound healing. The expression of EIIIA+ fibronectin mRNA during wound healing, a fibronectin isoform that was highly expressed in embryonic tissue, suggests that this fibronectin isoform is involved functionally in corneal wound healing.

Alternative Splicing↗
PubMed1993

Changes in plasma fibronectin in children after elective repair of congenital heart defects.

Plasma fibronectin is an attachment protein important for maintaining capillary integrity and host defense mechanisms. Depletion of plasma fibronectin has been shown to occur in adults after septic shock, major trauma, and burns. Limited laboratory and clinical studies suggest a correlation between decreased plasma fibronectin levels and increased pulmonary capillary permeability and tissue perfusion. Mild and transient plasma fibronectin depletion has been observed in adults after cardiovascular operations. We measured plasma fibronectin by immunoturbidometric assay in 20 children (age 6 months to 12 years) undergoing repair of congenital heart defects. Plasma fibronectin levels immediately after operations and daily thereafter were compared with the preoperative values. Plasma fibronectin declined on postoperative days 1, 2, 3, 4, and 5 (p < 0.05). A nadir was reached on day 3 with a tendency toward recovery thereafter. Patients with a therapeutic intervention score of more than 35 had greater magnitude of plasma fibronectin decline than those with a score of less than 35 at 24 hours after the operation (p < 0.005). We conclude that (1) significant and prolonged plasma fibronectin depletion occurs after cardiovascular operations in children; and (2) postoperative plasma fibronectin depletion is associated with increasingly complex surgical intervention. Reduced plasma fibronectin synthesis and more extensive operations for congenital heart defects are likely reasons for children being more susceptible than adults to plasma fibronectin depletion after cardiovascular operations.

Capillary Permeability↗
PubMed1978

High molecular weight, cell surface-associated glycoprotein (fibronectin) lost in malignant transformation.

Fibronectin is a polymorphic glycoprotein found in blood and tissues of vertebrates and in cultures of adherent vertebrate cells. There are several forms of fibronectin is composed of two high molecular weight subunits held together by forms found in tissues and on and around the surfaces of cultured cells. Soluble fibronectin is composed of two high molecular weight subunits held together by disulfide bonds. Insoluble fibronectin may be covalently cross-linked in larger complexes. Fibronectin has affinities for collagen, fibrin, heparin, and cell surfaces. In culture, fibronectin in growth medium may mediate attachment of cells to substratum, and fibronectin synthesized by cells may mediate adhesion to substratum. The widespread occurrence of fibronectin in basal lamina indicates that may different cell types in vivo abut against a fibronectin-containing matrix. Cultured transformed cells usually lack cell-surface fibronectin, also called large, external transformation-sensitive (LETS) protein. The failure of transformed cells to synthesize or bind fibronectin is paralleled (at least in some systems) by failures to synthesize or bind collagen and proteoglycans. Abnormal synthesis of fibronectin and other matrix components and abnormal interactions with the tissue matrix may account for several phenotypic characteristics of transformed cultured cells and for some of the malignant behavior of neoplastic cells in vivo.

Amino Acids↗
PubMed1979

Cross-linking of fibronectin to collagen by blood coagulation Factor XIIIa.

Soluble fibronectin is found in body fluids and media of adherent cultured cells and binds to fibrin and collagen. Insoluble fibronectin is found in tissue stroma and in extracellular matrices of cultured cells. Fibronectin is a substrate for Factor XIIIa (plasma transglutaminase) and can be cross-linked by Factor XIIIa to itself and the the alpha-chain of fibrin. We used sodium dodecyl sulfate-polyacrylamide gel electrophoresis to investigate Factor XIIIa-mediated crosslinking of fibronectin to collagen. At O degrees or 37 degrees C, fibronectin could be cross-linked to iodinated cyanogen bromide fragment 7 of the alpha 1(I) chain. At 22 degrees or 37 degrees C, fibronectin could be cross-linked to isolated alpha 1(I) chains of type I collagen. Fibronectin could also be crosslinked to types I and III collagen, but only at 37 degrees C. alpha 1(I)-CB7, alpha 1(I) collagen chains, type I collagen, type III collagen, and fibrin all blocked cross-linking between 125I-alpha 1 (I)-CB7 and fibronectin. alpha 1(I)-CB7 blocked cross-linking between fibronectin and fibrin. These results indicate that the determinants of fibronectin-fibrin and fibronectin-collagen binding and cross-linking are similar. Cross-linking of fibronectin to collagen likely occurs in vivo and may be important for normal wound healing, collagen fibrillogenesis, and embryogenesis.

Binding Sites↗
PubMed2000

Outside-in signalling of fibronectin stimulates cardiomyocyte hypertrophy in cultured neonatal rat ventricular myocytes.

Cardiac hypertrophy involves the accumulation of extracellular matrix proteins, such as fibronectin, leading to increasing myocardial stiffness, ventricular dysfunction and heart failure. To better understand the possible role of extracellular matrix-evoked intracellular signalling in ventricular myocytes, we investigated the effect of fibronectin on myocyte hypertrophic responses using cell culture models. Cell size in myocytes cultured on fibronectin-coated dishes was three times larger than that grown on non-coated dishes. However, the number of cells on fibronectin-coated dishes was not changed throughout the experiment. Protein synthesis was significantly increased by fibronectin, as were synthesis of atrial and brain natriuretic peptides. Fibronectin also elicited actin reorganization, co-localization of beta 1 integrin and vinculin, formation of focal adhesions and tyrosine phosphorylation of focal adhesion kinase in myocytes. These fibronectin-mediated effects were inhibited in a dose-dependent manner by GRGDSP, a competitive antagonist of the fibronectin receptors; GRGDSP had no effect on cell number or viability. Blocking antibody for beta 1 and beta 3 integrin significantly suppressed fibronectin-induced secretion of natriuretic peptides. Myocyte hypertrophy was observed in myocyte-nonmyocyte co-culture that reflects more closely the myocyte environment in vivo. GRGDSP may also suppress the myocyte hypertrophic response in the co-culture. These findings demonstrate that the interaction of fibronectin and RGD-dependent integrins is involved in the hypertrophic responses of myocyte in vitro, and suggest that extracellular matrix proteins such as fibronectin are not merely passive adhesive molecules but are active participants in processes leading to myocyte hypertrophy.

Animals↗
PubMed1991

Expression of fibronectin receptor (integrin) in the uterus of rats in relation to the estrous cycle.

The expression and localization of fibronectin receptor (integrin), fibronectin, laminin and collagen type IV in the endometrium of the rat uterus during each period of the estrous cycle were investigated by immunofluorescent microscopy. Fibronectin receptor was observed at the epithelial cells of the endometrium and at vascular endothelial cells. At proestrus, when epithelial cells actively migrate, fibronectin receptor was observed at the basal and lateral epithelial cell surfaces. During estrus, fibronectin receptor had begun to disappear, little fibronectin receptor was observed at metestrus or diestrus. No prominent changes in the localization of fibronectin (seen at the vascular endothelial cells and in the stroma) or of laminin and collagen type IV (seen at the muscles and at the basement membranes of the epithelial and vascular endothelial cells) were observed in relation to the estrous cycle. Thus, uterine epithelial cells, like epithelial cells of the healing cornea, increase their expression of fibronectin receptor during active migration, probably facilitating their attachment to stromal fibronectin. This fibronectin-fibronectin receptor mechanism may underlie epithelial repair, whether the defect results from physiological processes or from an insult.

Animals↗