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Interaction between fibrinogen and insulin-like growth factor-binding protein-1 in human plasma under physiological conditions

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Abstract

Fibrinogen is a plasma glycoprotein and one of the principle participants in blood coagulation. It interacts with many proteins during formation of a blood clot, including insulin-like growth factors (IGFs) and their binding proteins (IGFBP). Fibrinogen complexes were found as minor fractions in fibrinogen preparations independently of the coagulation process, and their presence influences the kinetics of polymerization. The idea of this work was to investigate whether fibrinogen in human plasma interacts with IGFBPs independently of the tissue injury or coagulation process. The results have shown that fibrinogen forms complexes with IGFBP-1 under physiological conditions. Several experimental approaches have confirmed that complexes are co-isolated with fibrinogen from plasma, they are relatively stable, and they appear as a general feature of human plasma. Several other experiments excluded the possibility that alpha-2 macroglobulin/IGFBP-1 complexes or IGFBP-1 oligomers contributed to IGFBP-1 immunoreactivity. The role of fibrinogen/IGFBP-1 complexes is still unknown. Further investigation in individuals expressing both impaired glucose control and coagulopathy could contribute to identification and understanding of their possible physiological role.

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Abbreviations

ConA:

lectin from Canavalia ensiformis

IGF:

insulin-like growth factor

IGFBP:

IGF-binding protein

PBS:

phosphate buffered saline

References

  1. Schmidt, D., and Brennan, S. O. (2007) Modified form of the fibrinogen Bβ chain (des-Gln Bβ), a potential longlived marker of pancreatitis, Clin. Chem., 53, 2105–2111.

    CAS  Google Scholar 

  2. Tennent, G. A., Brennan, S. O., Stangou, A. J., O’Grady, J., Hawkins, P. N., and Pepys, M. B. (2007) Human plasma fibrinogen is synthesized in the liver, Blood, 109, 1971–1974.

    Article  CAS  PubMed  Google Scholar 

  3. Chapin, J. C., and Hajjar, K. A. (2015) Fibrinolysis and the control of blood coagulation, Blood Rev., 29, 17–24.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. McMullin, N. R., Kauvar, D. S., Currier, H. M., Baskin, T. W., Pusateri, A. E., and Holcomb, J. B. (2006) The clinical and laboratory response to recombinant factor VIIa in trauma and surgical patients with acquired coagulopathy, Curr. Surg., 63, 246–251.

    Article  PubMed  Google Scholar 

  5. Asselta, R., Duga, S., and Tenchini, M. L. (2006) The molecular basis of quantitative fibrinogen disorders, J. Thromb. Haemost., 4, 2115–2129.

    Article  CAS  PubMed  Google Scholar 

  6. Becatti, M., Marcucci, R., Bruschi, G., Taddei, N., Bani, D., Gori, A. M., Giusti, B., Gensini, G. F., Abbate, R., and Fiorillo, C. (2014) Oxidative modification of fibrinogen is associated with altered function and structure in the subacute phase of myocardial infarction, Arterioscler. Thromb. Vasc. Biol., 34, 1355–1361.

    Article  CAS  PubMed  Google Scholar 

  7. Dunn, E. J., Philippou, H., Ariens, R. A. S., and Grant, P. J. (2006) Molecular mechanisms involved in the resistance of fibrin to clot lysis by plasmin in subjects with type 2 diabetes mellitus, Diabetologia, 49, 1071–1080.

    Article  CAS  PubMed  Google Scholar 

  8. Brennan, S. O. (2015) Variation of fibrinogen oligosaccharide structure in the acute phase response: possible hemorrhagic implications, Biochim. Biophys. Acta, 3, 221–226.

    Google Scholar 

  9. Scott, E. M., Ariens, R. A. S., and Grant, P. J. (2004) Genetic and environmental determinants of fibrin structure and function, Arterioscler. Thromb. Vasc. Biol., 24, 1558–1566.

    Article  CAS  PubMed  Google Scholar 

  10. Schneider, D. J., Taatjes, D. J., Howard, D. B., and Sobel, B. E. (1999) Increased reactivity of platelets induced by fibrinogen independent of its binding to the IIb-IIIa surface glycoprotein, J. Am. Coll. Cardiol., 33, 261–266.

    Article  CAS  PubMed  Google Scholar 

  11. Makogonenko, E., Tsurupa, G., Ingham, K., and Medved, L. (2002) Interaction of fibrin(ogen) with fibronectin: further characterization and localization of the fibronectinbinding site, Biochemistry, 41, 7907–7913.

    Article  CAS  PubMed  Google Scholar 

  12. Dowling, P., Palmerini, V., Henry, M., Meleady, P., Lynch, V., Ballot, J., Gullo, G., Crown, J., Moriarty, M., and Clynes, M. (2014) Transferrin-bound proteins as potential biomarkers for advanced breast cancer patients, Biochim. Biophys. Acta, 2, 24–30.

    Google Scholar 

  13. Talens, S., Leebeek, F. W. G., Demmers, J. A. A., and Rijken, D. C. (2012) Identification of fibrin clot-bound plasma proteins, PLoS One, 7, e41966.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Sahni, A., Simpson-Haidaris, P. J., Sahni, S. K., Vaday, G. G., and Francis, C. W. (2008) Fibrinogen synthesized by cancer cells augments the proliferative effect of fibroblast growth factor-2 (FGF-2), J. Thromb. Haemost., 6, 176–183.

    Article  CAS  PubMed  Google Scholar 

  15. Martino, M. M., Briquez, P. S., Ranga, A., Lutolf, M. P., and Hubbell, J. A. (2013) Heparin-binding domain of fibrin(ogen) binds growth factors and promotes tissue repair when incorporated within a synthetic matrix, Proc. Natl. Acad. Sci. USA, 110, 4563–4568.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Haase, I., Evans, R., Pofahl, R., and Watt, F. M. (2003) Regulation of keratinocyte shape, migration and wound epithelialization by IGF-1and EGF-dependent signaling pathways, J. Cell Sci., 116, 3227–3238.

    Article  CAS  PubMed  Google Scholar 

  17. Werner, S., and Grose, R. (2003) Regulation of wound healing by growth factors and cytokines, Physiol. Rev., 83, 835–870.

    CAS  PubMed  Google Scholar 

  18. Annunziata, M., Granata, R., and Ghigo, E. (2011) The IGF system, Acta Diabetol., 48, 1–9.

    Article  CAS  PubMed  Google Scholar 

  19. LeRoith, D., and Roberts, C. T., Jr. (2003) The insulin-like growth factor system and cancer, Cancer Lett., 195, 127–137.

    Article  CAS  PubMed  Google Scholar 

  20. Firth, S. M., and Baxter, R. C. (2002) Cellular actions of the insulin-like growth factor binding proteins, Endocrinol. Rev., 23, 824–854.

    Article  CAS  Google Scholar 

  21. Lee, P. D. K., Conover, C. A., and Powell, D. R. (1993) Regulation and function of insulin-like growth factor-binding protein-1, Exp. Biol. Med., 204, 4–29.

    Article  CAS  Google Scholar 

  22. Marcinkiewicz, M., and Gordon, P. V. (2008) A role for plasmin in platelet aggregation: differential regulation of IGF release from IGF-IGFBP complexes? Growth Horm. IGF Res., 18, 325–334.

    Article  CAS  PubMed  Google Scholar 

  23. Campbell, P. G., Novak, J. F., Yanosick, T. B., and McMaster, J. H. (1992) Involvement of the plasmin system in dissociation of the insulin-like growth factor-binding protein complex, Endocrinology, 130, 1401–1412.

    CAS  PubMed  Google Scholar 

  24. Campbell, P. G., Durham, S. K., Hayes, J. D., Suwanichkul, A., and Powell, D. R. (1999) Insulin-like growth factor-binding protein-3 binds fibrinogen and fibrin, J. Biol. Chem., 274, 30215–30221.

    Article  CAS  PubMed  Google Scholar 

  25. Huang, L., and Lord, S. T. (2013) The isolation of fibrinogen monomer dramatically influences fibrin polymerization, Thromb. Res., 131, 258–263.

    Article  Google Scholar 

  26. Cohn, E. J., Strong, L. E., Hughes, W. L., Jr., Mulford, D. J., Ashworth, J. N., Melin, M., and Taylor, H. L. (1946) Preparation and properties of serum and plasma proteins. IV. A system for the separation into fractions of the protein and lipoprotein components of biological tissues and fluids, J. Am. Chem. Soc., 63, 459–475.

    Article  Google Scholar 

  27. Fowell, A. H. (1955) Turbidimetric method of fibrinogen assay, Am. J. Clin. Pathol., 25, 340–342.

    CAS  PubMed  Google Scholar 

  28. Lagundzin, D., Masnikosa, R., Miljus, G., Robajac, D., and Nedic, O. (2010) An investigation of the different molecular forms of IGFBP-1 using immobilized metal-, immuno-, and lectin-affinity chromatography, J. Serb. Chem. Soc., 75, 1481–1489.

    Article  CAS  Google Scholar 

  29. Westwood, M., Aplin, J. D., Collinge, I. A., Gill, A., White, A., and Gibson, J. M. (2001) α2-Macroglobulin: a new component in the insulin-like growth factor/insulin-like growth factor binding protein-1 axis, J. Biol. Chem., 276, 41668–41674.

    Article  CAS  PubMed  Google Scholar 

  30. Sunderic, M., Malenkovic, V., and Nedic, O. (2015) Complexes between insulin-like growth factor binding proteins and alpha-2-macroglobulin in patients with tumor, Exp. Mol. Pathol., 98, 173–177.

    Article  CAS  PubMed  Google Scholar 

  31. Shibuya, H., Sakai, K., Kabir-Salmani, M., Wachi, Y., and Iwashita, M. (2011) Polymerization of insulin-like growth factor-binding protein-1 (IGFBP-1) potentiates IGF-I actions in placenta, J. Cell. Physiol., 226, 434–439.

    Article  CAS  PubMed  Google Scholar 

  32. Sakai, K., Busby, W. H., Jr., Clarke, J. B., and Clemmons, D. R. (2001) Tissue transglutaminase facilitates the polymerization of insulin-like growth factor-binding protein-1 (IGFBP-1) and leads to loss of IGFBP-1 ability to inhibit insulin-like growth factor-I-stimulated protein synthesis, J. Biol. Chem., 276, 8740–8745.

    Article  CAS  PubMed  Google Scholar 

  33. Masnikosa, R., Zivkovic, B., and Nedic, O. (2009) IGFBP-1 forms associates with placental cell membranes, J. Serb. Chem. Soc., 74, 707–716.

    Article  CAS  Google Scholar 

  34. Dunn, S., and Spiro, R. (1967) The α2-macroglobulin of human plasma, J. Biol. Chem., 242, 5549–5555.

    CAS  PubMed  Google Scholar 

  35. Adamczyk, B., Struwe, W. B., Ercan, A., Nigrovic, P. A., and Rudd, P. M. (2013) Characterization of fibrinogen glycosylation and its importance for serum/plasma N-glycome analysis, J. Proteome Res., 12, 444–454.

    Article  CAS  PubMed  Google Scholar 

  36. Krusius, T., Finne, J., and Rauvala, H. (1976) The structural basis of the different affinities of two types of acidic Nglycosidic glycopeptides for concanavalin A-Sepharose, FEBS Lett., 71, 117–120.

    Article  CAS  Google Scholar 

  37. Rajaram, S., Baylink, D. J., and Mohan, S. (1997) Insulinlike growth factor-binding proteins in serum and other biological fluids: regulation and functions, Endocrinol. Rev., 18, 801–831.

    CAS  Google Scholar 

  38. Hwa, V., Oh, Y., and Rosenfeld, R. G. (1999) The insulinlike growth factor-binding protein (IGFBP) superfamily, Endocrinol. Rev., 20, 761–787.

    CAS  Google Scholar 

  39. Weber, M. M., Spottl, G., Gossl, C., and Engelhardt, D. (1999) Characterization of human insulin-like growth factor-binding proteins by two-dimensional polyacrylamide gel electrophoresis and western ligand blot analysis, J. Clin. Endocrinol. Metab., 84, 1679–1684.

    CAS  PubMed  Google Scholar 

  40. Hjortebjerg, R., and Frystyk, J. (2013) Determination of IGFs and their binding proteins, Best Pract. Res. Clin. Endocrinol. Metab., 27, 771–781.

    Article  CAS  PubMed  Google Scholar 

  41. Brandt, K., Grunler, J., Brismar, K., and Wang, J. (2015) Effects of IGFBP-1 and IGFBP-2 and their fragments on migration and IGF-induced proliferation of human dermal fibroblasts, Growth Horm. IGF Res., 25, 34–40.

    Article  CAS  PubMed  Google Scholar 

  42. Jones, J., Gockerman, A., Busby, W. H., Jr., Wright, G., and Clemmons, D. R. (1993) Insulin-like growth factor binding protein 1 stimulates cell migration and bind to the α5β1 integrin by means of its Arg-Gly-Asp sequence, Proc. Natl. Acad. Sci. USA, 90, 10553–10557.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Ramos-Mozo, P., Rodriguez, C., Pastor-Vargas, C., Blanco-Colio, L. M., Martinez-Gonzalez, J., Meilhac, O., Michel, J.-B., Vega De Cenga, M., Egido, J., and MartinVentura, J. L. (2012) Plasma profiling by a protein array approach identifies IGFBP-1 as a novel biomarker of abdominal aortic aneurysm, Atherosclerosis, 221, 544–550.

    Article  CAS  PubMed  Google Scholar 

  44. Kobayashi, M., Kawase, T., Horimizu, M., Okuda, K., Wolff, L. F., and Yoshie, H. (2012) A proposed protocol for the standardized preparation of PRF membranes for clinical use, Biologicals, 40, 323–329.

    Article  CAS  PubMed  Google Scholar 

  45. Aneke-Nash, C. S., Parrinello, C. M., Rajpathak, S. N., Rohan, T. E., Strotmeyer, E. S., Kritchevsky, S. B., Psaty, B. M., Buzikova, P., Kizer, J. R., Newman, A. B., Strickler, H. D., and Kaplan, R. C. (2015) Changes in insulin-like growth factor-I and its binding proteins are associated with diabetes mellitus in older adults, J. Am. Geriatr. Soc., 63, 902–909.

    Article  PubMed  Google Scholar 

  46. Carr, M. E. (2001) Diabetes mellitus a hypercoagulable state, J. Diabetes Complicat., 15, 44–54.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to N. Gligorijević.

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Published in Russian in Biokhimiya, 2016, Vol. 81, No. 2, pp. 231–237.

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM15-283, December 27, 2015.

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Gligorijević, N., Nedić, O. Interaction between fibrinogen and insulin-like growth factor-binding protein-1 in human plasma under physiological conditions. Biochemistry Moscow 81, 135–140 (2016). https://doi.org/10.1134/S0006297916020073

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  • DOI: https://doi.org/10.1134/S0006297916020073

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