Disease relevance of Fn1

• The antisense fibronectin oligos may provide a useful approach for reducing vascular lesions in diabetic retinopathy [1].
• It is interesting that MC slowly underwent apoptosis after infection with a retrovirus that continuously suppressed fibronectin synthesis [2].
• A progressive increase in fibronectin synthesis was found in metabolically labeled cortical or glomerular culture at week 8 or 16, correlating with the degree of glomerulosclerosis and interstitial fibrosis [3].
• Proteinuria, glomerular matrix protein staining, and glomerular mRNA levels for transforming growth factor-beta 1 (TGF-beta 1), fibronectin, and plasminogen activator inhibitor type 1 (PAI-1) were evaluated at day 6 [4].
• Alternative splicing of fibronectin mRNAs in chondrosarcoma cells: role of far upstream intron sequences [5].

Psychiatry related information on Fn1

• Thus, FN appears to have a critical role in the host defense mechanisms against group B streptococci [6].
• The discovery of astrocyte fibronectin expression as a potential regulated target for chronic alcohol abuse may be useful in understanding, preventing, and treating some brain disorders associated with alcohol abuse and alcoholism [7].
• Our results suggest that embryonic fibronectins synthesized within the nerve contribute to the permissiveness of the peripheral nervous system to axon regrowth and a mechanism by which alternative splicing of the V region in fibronectin mRNA could enhance nervous system regeneration [8].
• Fibronectin appears to be present in Senile Plaques of Alzheimer's disease brains [9].
• Collagen and fibronectin in a healing skeletal muscle injury. An immunohistological study of the effects of physical activity on the repair of injured gastrocnemius muscle in the rat [10].

High impact information on Fn1

• TAG-1 has six immunoglobulin-like domains and four fibronectin type III-like repeats and is structurally similar to other immunoglobulin-like proteins expressed on developing axons [11].
• Restriction mapping and DNA sequencing of these clones establish the sequence of the C-terminal 35% of rat fibronectin, covering the cell-, heparin-, and fibrin-binding domains [12].
• Three different fibronectin mRNAs arise by alternative splicing within the coding region [12].
• Attachment of rat hepatocytes to collagen, which occurs without the aid of fibronectin, was found to be a time-dependent reaction characterized by an initial lag phase of 10-20 min before stable attachment bonds began to form [13].
• Attempts to identify this protein on monocytes with conventional heteroantisera directed against fibronectin, complement components, fibrinogen, collagen, tubulin and actin have failed [14].

Chemical compound and disease context of Fn1

• To determine whether BM thickening of retinal capillaries could be prevented by down regulating synthesis of fibronectin, an ECM component, we used antisense oligos targeted against translation initiation site of the fibronectin transcript in galactose-fed rat, an animal model of diabetic retinopathy [1].
• Potential mechanism of fibronectin deposits in acute renal failure induced by mercuric chloride [15].
• ALT-711 treatment attenuated expression of vascular endothelial growth factor and the extracellular matrix proteins, fibronectin and laminin, in association with reduced albuminuria [16].
• It significantly suppressed renal malondialdehyde (MDA), microalbuminuria, glomerular hypertrophy, mesangial expansion, and the upregulation of renal TGF-beta1, fibronectin, and collagen in STZR without significantly affecting plasma glucose [17].
• Chronic administration of melatonin (n = 6) and taurine (n = 6) prevented increases in glomerular TGF-beta1 and fibronectin mRNAs and proteinuria without having effect on blood glucose [18].

Biological context of Fn1

• Comparison of these sequences and the exon structures of the fibronectin and tissue plasminogen activator genes indicates that exons encoding type I and type II repeats have reassorted during evolution [19].
• We also report analyses of the extreme 5' and 3' ends of the fibronectin gene including the promoter region and the exon encoding the prepro sequence of fibronectin and we show that the gene is transcribed from a single initiation site to a single polyadenylation site [19].
• In order to test this hypothesis, we have isolated clones spanning approximately half of the fibronectin gene from a Fisher rat genomic library; blot hybridization analyses reveal the presence of only one fibronectin gene in the haploid rat genome [20].
• In the present experiments, we have studied the regulation of fibronectin splicing in primary sinusoidal endothelial cells by transfecting a minigene containing the EIIIA exon and its flanking introns, driven by various promoters [21].
• The unique dimerization pattern of (V + C)(-) fibronectin does not prevent matrix formation yet is consistent with this isoform having specialized properties in situ that are important for either the structural organization and biomechanical properties of cartilage or the regulation of a chondrocytic phenotype [22].

Anatomical context of Fn1

• Both are excluded from mRNA in liver cells and are, therefore, absent from plasma fibronectin [23].
• The results indicate that fibronectin splicing in endothelial cells from normal liver is in part promoter-dependent [21].
• Downregulation of fibronectin overexpression reduces basement membrane thickening and vascular lesions in retinas of galactose-fed rats [1].
• Aortic smooth muscle cells (SMCs) of diabetic animals have unique properties, including the overexpression of transforming growth factor-beta (TGF-beta) type II receptor, fibronectin, and platelet-derived growth factor beta-receptor [24].
• Here we found that PGE(2) enhanced extracellular Fn assembly in rat primary osteoblasts, as shown by immunofluorescence staining and enzyme-linked immunosorbent assay [25].

Associations of Fn1 with chemical compounds

• Local administration of PGE(2) or 17-phenyl trinor PGE(2) into the metaphysis of the tibia via the implantation of a needle cannula significantly increased the Fn and alpha5beta1 integrin immunostaining and bone volume of secondary spongiosa in tibia [25].
• After 2 months of galactose-feeding, intravitreal administration of 3 micro mol/l antisense fibronectin oligos was initiated at monthly intervals for 3 months [1].
• Coexpression of LynA devoid of C-terminal negative regulatory tyrosine in mCsk cells successfully restored Fn-mediated podosome formation and cell migration [26].
• Prostaglandin E2 stimulates fibronectin expression through EP1 receptor, phospholipase C, protein kinase Calpha, and c-Src pathway in primary cultured rat osteoblasts [25].
• Additional studies found that the mechanism for the motility-suppressive effects of fibulin-1 does not involve perturbations of interactions between alpha5beta1 or alpha4 integrins, or heparan sulfate proteoglycans with FN [27].

Physical interactions of Fn1

• The effect of TGF-beta was exerted by stabilizing fibronectin mRNA without affecting the promoter activity and required de novo protein synthesis [28].
• PAK1 and ERK1/2 co-immunoprecipitated from rat aortic smooth muscle cells (SMC) plated on fibronectin, and the two proteins co-localized in membrane ruffles and adhesion complexes following PDGF-BB or sphingosine 1-phosphate treatment, respectively [29].
• BACKGROUND: G10BP, a serum-inducible factor, represses the transcription of the fibronectin gene through binding to the G-rich sequences in the promoter excluding Sp1 from binding to these sequences [30].
• Tenascin-C (TN-C) is a matrix molecule reported to bind some cell lines and to inhibit adhesion of some cell types to fibronectin [31].
• The effect of NGF is specific since the amount of a 150-kDa fibronectin-binding integrin alpha subunit remained unchanged [32].

Enzymatic interactions of Fn1

• The presence of talin and extracellular matrix receptor in podosomes together with the adhesive properties of these actin-containing structures argues against the hypothesis that pp60src affects the interaction of actin with the plasma membrane by phosphorylating the fibronectin receptor and/or other associated proteins [33].

Regulatory relationships of Fn1

• At the mechanistic level, Ca(2+) chelator (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl ester)), phosphatidylinositol-phospholipase C inhibitor (U73122), or Src inhibitor (PP2) attenuated the PGE(2)-induced Fn expression [25].
• In addition, TGF beta RII/Fc diminished the TGF-beta 1-induced production of EIIIA-positive fibronectin in cultured normal rat kidney cells [34].
• FRT cells secrete and expose on the plasma membrane the tissue-type plasminogen activator and, in serum-free cultures, plasminogen induces a rapid loss of FN fibrils [35].
• Transactivation of EGF receptor induced by angiotensin II regulates fibronectin and TGF-beta gene expression via transcriptional and post-transcriptional mechanisms [36].
• Attachment assays showed that FGF-1 treatment enhanced type II cell adhesion to fibronectin [37].

Other interactions of Fn1

• This is in agreement with the observation that a great reduction in FN degradation is observed if the cells are pre-incubated with carboxypeptidase B, which prevents plasminogen binding to the cells [35].
• Here, we examined whether fibronectin (FN) and FGF can cooperate for neuronal adhesion and neurite outgrowth [38].
• These results indicate that in the FN remodeling process, occurring during FRT epithelium maturation, both plasmin-dependent (tPA activated) and plasmin-independent proteolytic activities are involved [35].
• Furthermore, increased level of the MMP-2 transcript was followed by disappearance of fibronectin [39].
• It is well established that alpha2beta1 integrin functions as a receptor for collagen and laminin; whereas alpha4beta1 integrin binds fibronectin and vascular cell adhesion molecule-1 (VCAM-1) [40].

Analytical, diagnostic and therapeutic context of Fn1

• Northern blot analysis of total RNA revealed time-dependent induction of alpha1(I) collagen, alpha1(III) collagen, alpha1(IV) collagen, fibronectin, and laminin by stretch/relaxation, with maximal increases occurring between 12 and 24 h [41].
• PGE(2) also increased the protein levels of Fn by using Western blotting analysis [25].
• SDS-PAGE and immunoblot analyses of the resulting conditioned media suggest that the I-10 segment must either be present in both monomeric subunits of fibronectin or absent from both subunits for efficient dimerization to occur [22].
• In the present study, we investigated ED-B FN expression in chronic allograft nephropathy and its relationship with endothelins (ET) [42].
• The third species was analysed by denaturing PAGE, immunoblotting, proteinase digestion and N-terminal-sequence analyses, and shown to consist of a complex between alpha 1-m and fibronectin [43].

References