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Gene Review

Fn1  -  fibronectin 1

Rattus norvegicus

Synonyms: FIBNEC, FN, Fibronectin, fn-1
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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


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


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


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


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].


  1. Downregulation of fibronectin overexpression reduces basement membrane thickening and vascular lesions in retinas of galactose-fed rats. Roy, S., Sato, T., Paryani, G., Kao, R. Diabetes (2003) [Pubmed]
  2. Knockdown of fibronectin induces mitochondria-dependent apoptosis in rat mesangial cells. Wu, D., Chen, X., Guo, D., Hong, Q., Fu, B., Ding, R., Yu, L., Hou, K., Feng, Z., Zhang, X., Wang, J. J. Am. Soc. Nephrol. (2005) [Pubmed]
  3. TGF-beta 1 in glomerulosclerosis and interstitial fibrosis of adriamycin nephropathy. Tamaki, K., Okuda, S., Ando, T., Iwamoto, T., Nakayama, M., Fujishima, M. Kidney Int. (1994) [Pubmed]
  4. t-PA promotes glomerular plasmin generation and matrix degradation in experimental glomerulonephritis. Haraguchi, M., Border, W.A., Huang, Y., Noble, N.A. Kidney Int. (2001) [Pubmed]
  5. Alternative splicing of fibronectin mRNAs in chondrosarcoma cells: role of far upstream intron sequences. Flanagan, M., Liang, H., Norton, P.A. J. Cell. Biochem. (2003) [Pubmed]
  6. Fibronectin enhances the opsonic and protective activity of monoclonal and polyclonal antibody against group B streptococci. Hill, H.R., Shigeoka, A.O., Augustine, N.H., Pritchard, D., Lundblad, J.L., Schwartz, R.S. J. Exp. Med. (1984) [Pubmed]
  7. Differential fibronectin expression in activated C6 glial cells treated with ethanol. Ren, L.Q., Garrett, D.K., Syapin, M., Syapin, P.J. Mol. Pharmacol. (2000) [Pubmed]
  8. Embryonic fibronectins are up-regulated following peripheral nerve injury in rats. Mathews, G.A., Ffrench-Constant, C. J. Neurobiol. (1995) [Pubmed]
  9. Fibronectin modulation by A beta amyloid peptide (25-35) in cultured astrocytes of newborn rat cortex. Moreno-Flores, M.T., Martín-Aparicio, E., Salinero, O., Wandosell, F. Neurosci. Lett. (2001) [Pubmed]
  10. 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. Lehto, M., Duance, V.C., Restall, D. The Journal of bone and joint surgery. British volume. (1985) [Pubmed]
  11. The axonal glycoprotein TAG-1 is an immunoglobulin superfamily member with neurite outgrowth-promoting activity. Furley, A.J., Morton, S.B., Manalo, D., Karagogeos, D., Dodd, J., Jessell, T.M. Cell (1990) [Pubmed]
  12. Three different fibronectin mRNAs arise by alternative splicing within the coding region. Schwarzbauer, J.E., Tamkun, J.W., Lemischka, I.R., Hynes, R.O. Cell (1983) [Pubmed]
  13. Substrate adhesion of rat hepatocytes: mechanism of attachment to collagen substrates. Rubin, K., Höök, M., Obrink, B., Timpl, R. Cell (1981) [Pubmed]
  14. Monoclonal antibody with specificity for monocytes and neurons. Hogg, N., Slusarenko, M., Cohen, J., Reiser, J. Cell (1981) [Pubmed]
  15. Potential mechanism of fibronectin deposits in acute renal failure induced by mercuric chloride. Saball, E., Salvarrey, M., Serra, E., Picó, G., Elías, M.M. Mol. Cell. Biochem. (2001) [Pubmed]
  16. Attenuation of extracellular matrix accumulation in diabetic nephropathy by the advanced glycation end product cross-link breaker ALT-711 via a protein kinase C-alpha-dependent pathway. Thallas-Bonke, V., Lindschau, C., Rizkalla, B., Bach, L.A., Boner, G., Meier, M., Haller, H., Cooper, M.E., Forbes, J.M. Diabetes (2004) [Pubmed]
  17. Delayed treatment with lithospermate B attenuates experimental diabetic renal injury. Lee, G.T., Ha, H., Jung, M., Li, H., Hong, S.W., Cha, B.S., Lee, H.C., Cho, Y.D. J. Am. Soc. Nephrol. (2003) [Pubmed]
  18. Melatonin and taurine reduce early glomerulopathy in diabetic rats. Ha, H., Yu, M.R., Kim, K.H. Free Radic. Biol. Med. (1999) [Pubmed]
  19. Organization of the fibronectin gene provides evidence for exon shuffling during evolution. Patel, R.S., Odermatt, E., Schwarzbauer, J.E., Hynes, R.O. EMBO J. (1987) [Pubmed]
  20. A single rat fibronectin gene generates three different mRNAs by alternative splicing of a complex exon. Tamkun, J.W., Schwarzbauer, J.E., Hynes, R.O. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  21. Regulation of fibronectin splicing in sinusoidal endothelial cells from normal or injured liver. Chang, M.L., Chen, J.C., Alonso, C.R., Kornblihtt, A.R., Bissell, D.M. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  22. Absence of the I-10 protein segment mediates restricted dimerization of the cartilage-specific fibronectin isoform. Chen, H., Gu, D.N., Burton-Wurster, N., MacLeod, J.N. J. Biol. Chem. (2002) [Pubmed]
  23. Multiple sites of alternative splicing of the rat fibronectin gene transcript. Schwarzbauer, J.E., Patel, R.S., Fonda, D., Hynes, R.O. EMBO J. (1987) [Pubmed]
  24. Latent transforming growth factor-beta binding protein-1, a component of latent transforming growth factor-beta complex, accelerates the migration of aortic smooth muscle cells in diabetic rats through integrin-beta3. Kanzaki, T., Otabe, M. Diabetes (2003) [Pubmed]
  25. Prostaglandin E2 stimulates fibronectin expression through EP1 receptor, phospholipase C, protein kinase Calpha, and c-Src pathway in primary cultured rat osteoblasts. Tang, C.H., Yang, R.S., Fu, W.M. J. Biol. Chem. (2005) [Pubmed]
  26. Essential roles of Lyn in fibronectin-mediated filamentous actin assembly and cell motility in mast cells. Suzuki, T., Shoji, S., Yamamoto, K., Nada, S., Okada, M., Yamamoto, T., Honda, Z. J. Immunol. (1998) [Pubmed]
  27. Fibulin-1 suppression of fibronectin-regulated cell adhesion and motility. Twal, W.O., Czirok, A., Hegedus, B., Knaak, C., Chintalapudi, M.R., Okagawa, H., Sugi, Y., Argraves, W.S. J. Cell. Sci. (2001) [Pubmed]
  28. Angiotensin II-induced transactivation of epidermal growth factor receptor regulates fibronectin and transforming growth factor-beta synthesis via transcriptional and posttranscriptional mechanisms. Moriguchi, Y., Matsubara, H., Mori, Y., Murasawa, S., Masaki, H., Maruyama, K., Tsutsumi, Y., Shibasaki, Y., Tanaka, Y., Nakajima, T., Oda, K., Iwasaka, T. Circ. Res. (1999) [Pubmed]
  29. Adhesion stimulates direct PAK1/ERK2 association and leads to ERK-dependent PAK1 Thr212 phosphorylation. Sundberg-Smith, L.J., Doherty, J.T., Mack, C.P., Taylor, J.M. J. Biol. Chem. (2005) [Pubmed]
  30. The G10BP-1 gene encoding a GC box binding protein, is a target of Myc and Jun/Fos. Shirasuna, K., Takeuchi, A., Bando, T., Nakajima, T., Oda, K. Genes Cells (1999) [Pubmed]
  31. Tenascin-C in rat lung: distribution, ontogeny and role in branching morphogenesis. Young, S.L., Chang, L.Y., Erickson, H.P. Dev. Biol. (1994) [Pubmed]
  32. Nerve growth factor induces increased expression of a laminin-binding integrin in rat pheochromocytoma PC12 cells. Rossino, P., Gavazzi, I., Timpl, R., Aumailley, M., Abbadini, M., Giancotti, F., Silengo, L., Marchisio, P.C., Tarone, G. Exp. Cell Res. (1990) [Pubmed]
  33. Cell/substratum adhesions in RSV-transformed rat fibroblasts. Nermut, M.V., Eason, P., Hirst, E.M., Kellie, S. Exp. Cell Res. (1991) [Pubmed]
  34. Gene therapy by transforming growth factor-beta receptor-IgG Fc chimera suppressed extracellular matrix accumulation in experimental glomerulonephritis. Isaka, Y., Akagi, Y., Ando, Y., Tsujie, M., Sudo, T., Ohno, N., Border, W.A., Noble, N.A., Kaneda, Y., Hori, M., Imai, E. Kidney Int. (1999) [Pubmed]
  35. The role of proteases in fibronectin matrix remodeling in thyroid epithelial cell monolayer cultures. Nezi, L., Greco, D., Nitsch, L., Garbi, C. Biol. Chem. (2002) [Pubmed]
  36. Transactivation of EGF receptor induced by angiotensin II regulates fibronectin and TGF-beta gene expression via transcriptional and post-transcriptional mechanisms. Matsubara, H., Moriguchi, Y., Mori, Y., Masaki, H., Tsutsumi, Y., Shibasaki, Y., Uchiyama-Tanaka, Y., Fujiyama, S., Koyama, Y., Nose-Fujiyama, A., Iba, S., Tateishi, E., Iwasaka, T. Mol. Cell. Biochem. (2000) [Pubmed]
  37. Effect of growth factor-fibronectin matrix interaction on rat type II cell adhesion and DNA synthesis. Pagan, I., Khosla, J., Li, C.M., Sannes, P.L. Exp. Lung Res. (2002) [Pubmed]
  38. Synergistic activity of fibronectin and fibroblast growth factor receptors on neuronal adhesion and neurite extension through extracellular signal-regulated kinase pathway. Choung, P.H., Seo, B.M., Chung, C.P., Yamada, K.M., Jang, J.H. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  39. Role of TGF-beta1, extracellular matrix, and matrix metalloproteinase in the healing process of the pancreas after induction of acute necrotizing pancreatitis using arginine in rats. Kihara, Y., Tashiro, M., Nakamura, H., Yamaguchi, T., Yoshikawa, H., Otsuki, M. Pancreas (2001) [Pubmed]
  40. Integrin alpha2beta1 on rat myeloma cells modulates interaction of alpha4beta1 integrin with vascular cell adhesion molecule-1 but not fibronectin. Chan, B.M., Morris, V.L., Hangan-Steinman, D., Jarvie, B., Cialacu, M., Laansoo, J., Hunter, G., Wan, W., Uniyal, S. Journal of biomaterials science. Polymer edition. (2002) [Pubmed]
  41. Regulation of extracellular matrix by mechanical stress in rat glomerular mesangial cells. Yasuda, T., Kondo, S., Homma, T., Harris, R.C. J. Clin. Invest. (1996) [Pubmed]
  42. Endothelin-mediated oncofetal fibronectin expression in chronic allograft nephropathy. Siddiqui, I., Khan, Z.A., Lian, D., Jiang, J., Zhong, R., Garcia, B., Chakrabarti, S. Transplantation (2006) [Pubmed]
  43. Isolation and characterization of fibronectin-alpha 1-microglobulin complex in rat plasma. Falkenberg, C., Enghild, J.J., Thøgersen, I.B., Salvesen, G., Akerström, B. Biochem. J. (1994) [Pubmed]
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