Disease relevance of Fn1

• Fibrosis was characterized by deposition of collagens and fibronectin, persistent activation of PSCs, and up-regulation of pancreatic transforming growth factor beta1 [1].
• After 8 weeks of diabetes, the high-glucose-induced renal and glomerular hypertrophy, as well as the increased expression of extracellular matrix proteins such as collagen and fibronectin, was reduced in PKC-beta(-/-) mice [2].
• Indeed, we have recently demonstrated that peptides derived from sequences in fibronectin abrogate the T cell-mediated contact hypersensitivity (CHS) reactions in vivo [3].
• RGD-containing peptides and the RGD mimetic, compound SF-6,5, but not the Arg-Gly-Glu (RGE) peptide or the corresponding mimetic, specifically inhibited B16-F10 melanoma cell adhesion to immobilized VN and FN [4].
• Fibronectin-binding protein I of Streptococcus pyogenes is a promising adjuvant for antigens delivered by mucosal route [5].

High impact information on Fn1

• In spreading and migrating cells we find local periodic contractions of lamellipodia that depend on matrix rigidity, fibronectin binding and myosin light chain kinase (MLCK) [6].
• We show here that integrin alpha8beta1, its ligand fibronectin and the integrin-regulated focal adhesion kinase (FAK) co-localize to the apical hair-cell surface where stereocilia are forming [7].
• Antibodies to integrin alpha 4 inhibit spreading of WEHI 231 cells on V+ fibronectin [8].
• Using purified recombinant fibronectins we show that WEHI 231 lymphoid cells spread only on fibronectin containing the alternatively spliced V region [8].
• Lymphoid cells recognize an alternatively spliced segment of fibronectin via the integrin receptor alpha 4 beta 1 [8].

Chemical compound and disease context of Fn1

• However, in knockout cells, high glucose failed to induce hypertrophy and was severely limited in its capacity to stimulate fibronectin [9].
• Herein we discuss recent findings on the defective expression of integrin-type fibronectin receptors alpha4beta1 (VLA-4) and alpha5beta1 (VLA-5) in the non-obese diabetic (NOD) mouse, a murine model of autoimmune insulin-dependent diabetes mellitus [10].
• Cell surface phosphatidylinositol-anchored heparan sulfate proteoglycan initiates mouse melanoma cell adhesion to a fibronectin-derived, heparin-binding synthetic peptide [11].
• The effect of retinoic acid pretreatment on metastatic B16 melanoma cell adhesion in serum-free medium to tissue culture plastic precoated with fibronectin, laminin/nidogen, type I and type IV collagen was examined [12].
• Compared with vehicle controls, paricalcitol significantly attenuated renal interstitial fibrosis in mouse kidney after ureteral obstruction, as demonstrated by a reduced interstitial volume, decreased collagen deposition, and repressed mRNA expression of fibronectin and type I and type III collagens [13].

Biological context of Fn1

• A detailed analysis of the molecular mechanisms involved in N1 and N7 cell adhesion to ECM substrata was performed by using antibodies raised against the FN receptor and synthetic peptides variously competing with the FN or VN binding to integrin receptor (GRGDSP and GRGESP) [14].
• Furthermore, our data suggest that FN acts synergistically with IgE to prolong intracellular phosphorylation events and to enhance IgE-induced inflammatory cytokine production and BMMC survival [15].
• Whereas cytokines activated resting progenitor cells to migrate on ECM, cell migration speed was regulated by Fn concentration [16].
• Fibronectin splice variants containing the EIIIA and/or EIIIB exons are prominently expressed in the vasculature of a variety of human tumors but not in normal adult tissues [17].
• Costimulation of fibronectin receptor promotes Fc gamma R-mediated rescue of IL-3-dependent bone marrow-derived cells from apoptosis [18].

Anatomical context of Fn1

• Exogenous provision of RA or Fn to Raldh2(-/-) explants in whole mouse embryo culture restored vascular remodeling, visceral endoderm survival, as well as integrin alpha5 expression and its downstream signaling that controls endothelial growth [19].
• Parental cells and cells expressing wild-type PTP1B show similar morphology, are able to attach and spread on fibronectin, and form focal adhesions and stress fibers [20].
• FN-induced cytoskeletal rearrangement was retarded in PTP alpha-/- cells, with delayed filamentous actin stress fiber assembly and focal adhesion formation [21].
• However, these anti-adhesive treatments, while ineffective on Vrest of N7 cells, abolished in N1 cells the FN- or VN-induced hyperpolarization and neurite outgrowth, that appeared therefore strictly associated and integrin-mediated phenomena [14].
• These data suggest that FN-binding integrins on T cells play a role in the localization of T cells to sites of antigenic challenge in tissue [22].

Associations of Fn1 with chemical compounds

• Antibodies, as well as GRGDSP, abolished adhesion of N1 and N7 clones to FN and VN, revealing a similar implication of integrins in the adhesion of these clones to the ECM proteins [14].
• We demonstrate that the cells that transfer CHS to TNCB adhere to FN in the presence of Ca2+/Mg2+, and T-cell populations depleted of FN-adherent cells do not transfer immunity [22].
• Furthermore, these effects of FN are blocked specifically by RGD peptide or anti-VLA-4 mAb [18].
• FAK catalytic activity, proline-rich domains, and location in focal contacts were all required for proper allocation and patterning of FN matrix [23].
• High glucose also increased fibronectin message and protein [9].
• Analysis of beta1-integrin-receptor-null fibroblasts, blockage of cell surface integrin receptors that regulate fibronectin assembly and disruption of Rho kinase all result in suppressed deposition of both fibronectin and microfibrils [24].

Physical interactions of Fn1

• Cells lacking FAK in focal adhesions fail to translocate supramolecular complexes of integrin-bound FN and focal adhesion proteins along actin filaments to form mature fibrillar adhesions [23].
• The potential usefulness of fibronectin-binding protein I (Sfbl) of Streptococcus pyogenes as immunological adjuvant was assessed using ovalbumin (OVA) as a model antigen [5].
• Identification of the fibronectin-binding site on tissue transglutaminase will help to dissect the role of this protein in cell-matrix interactions [25].
• Furthermore, monoclonal antibody to the alpha 6 beta 1 complex effectively blocked the attachment of B16-BL6 cells to laminin but did not affect adhesion to fibronectin or type IV collagen [26].
• Expression of fibronectin and a fibronectin-binding molecule during preimplantation development in the mouse [27].

Enzymatic interactions of Fn1

• Nuclear detection of Smad3 and phosphorylated Smads within intraluminal fibroblasts coincided with increased intraluminal deposition of fibronectin and collagen [28].
• It was found that FCS and fibronectin stimulated phosphorylating activity of FAK in the cells at the logarithmic phase of growth, but were inefficient in the confluent cells [29].
• The protein appears to be located in focal contacts where it codistributes with beta 1 integrins. pp120 is distinct from the beta 1 subunit of integrins and from vinculin and alpha-actinin. pp120 is rapidly dephosphorylated in cells suspended by trypsinization but becomes rapidly phosphorylated in cells attaching and spreading on fibronectin [30].
• Effects of fibronectin cleaved by neuropsin on cell adhesion and migration [31].

Co-localisations of Fn1

• We compared the distribution of alpha 8 with alpha-smooth muscle actin (alpha SMA), fibronectin (alpha 8 ligand), and cytokeratin. alpha 8 co-localized with alpha SMA and fibronectin in the peribronchial and perivascular regions [32].
• We now show by confocal microscopy that tTG colocalizes with pericellular fibronectin in these cells, and by immunogold electron microscopy that the two proteins are found in clusters at the cell surface [33].
• Punctate immunoreactivity for fibronectin and laminin was found to be colocalized with NG2 on the surface of NG2 cells [34].

Regulatory relationships of Fn1

• FAK promotes organization of fibronectin matrix and fibrillar adhesions [23].
• These data demonstrate that trafficking of alphaIIb regulates adhesion between trophoblast cells and fibronectin as invasion of the endometrium commences [35].
• Reduction in fibronectin expression and alteration in cell morphology are coincident in NIH3T3 cells expressing a mutant E2F1 transcription factor [36].
• RESULTS: TGF-beta up-regulated FN mRNA accumulation in a time- and dose-dependent manner, which was completely inhibited by phosphatidylcholine-phospholipase C (PC-PLC) inhibitor and PKC inhibitors (calphostin-C and staurosporin) [37].
• Transition from condensation to overt cell differentiation is under both positive and negative control (Fig. 3). Syndecan blocks fibronectin and so blocks N-CAM accumulation, preventing accumulation of additional cell[38]

Other interactions of Fn1

• Interestingly, we found, using the calcium channel blocker, 2-APB (2-aminoethoxydiphenyl borate) and Lyn-/- BMMCs that both IgE- and IgE + Ag-induced adhesion to FN require extracellular calcium entry, whereas SF does not [15].
• Mast cells from c-kit mutant mice adhere to fibronectin on stimulation with phorbol 12-myristate 13-acetate (PMA), but not on stimulation with steel factor, indicating that stimulation of integrin adhesiveness requires activation of the c-kit protein tyrosine kinase [39].
• To directly test the function of EIIIA-FN, we generated EIIIA-null (EIIIA(-/-)) mice that lack the EIIIA exon and crossed them with apolipoprotein E (ApoE)-null (ApoE(-/-)) mice that develop arterial wall lesions [40].
• Furthermore, we showed that maspin directly increased endodermal cell adhesion to laminin matrix but not to fibronectin [41].
• Laminin, entactin/nidogen, and fibronectin immunoreactivities were similarly ubiquitous on tumor vessels [42].

Analytical, diagnostic and therapeutic context of Fn1

• In co-cultures on vitronectin of FN-null cells and beta(1)-null cells expressing a chimera with the extracellular domain of beta(1) and the cytoplasmic domain of beta(3), preferential assembly was by the chimera-expressing cells [43].
• We analysed the impact of increased MMP activity on a number of ECM molecules by Western blot analysis, but found that only fibronectin abundance was consistently reduced in the null lungs throughout development [44].
• Functional comparisons among the three integrins revealed that ligation of alpha5beta1 most efficiently strengthened blastocyst fibronectin-binding activity, while subsequent trophoblast cell migration was dependent primarily on the beta3-class integrins [35].
• The expression of FN receptor VLA-5 on IECs was examined by flow cytometry [45].
• Fibronectin expression was assessed by Northern analysis and enzyme-linked immunosorbent assay (ELISA) [9].

References