Download PDF
Thromb Haemost 1985; 53(02): 212-215
DOI: 10.1055/s-0038-1661276
Original Article
Schattauer GmbH Stuttgart

Fibrinogen Fragments X, Y, D and E Increase Levels of Plasma Fibrinogen and Liver mRNAs Coding for Fibrinogen Polypeptides in Rats

H M G Princen
1   The Gaubius Institute, Health Research Division TNO, Leiden, The Netherlands
,
H J Moshage
The Division of Gastrointestinal and Liver Disease, Dept. of Medicine, St. Radboud Hospital, University of Nijmegen, Nijmegen, The Netherlands
,
J J Emeis
1   The Gaubius Institute, Health Research Division TNO, Leiden, The Netherlands
,
H J W de Haard
The Division of Gastrointestinal and Liver Disease, Dept. of Medicine, St. Radboud Hospital, University of Nijmegen, Nijmegen, The Netherlands
,
W Nieuwenhuizen
1   The Gaubius Institute, Health Research Division TNO, Leiden, The Netherlands
,
S H Yap
The Division of Gastrointestinal and Liver Disease, Dept. of Medicine, St. Radboud Hospital, University of Nijmegen, Nijmegen, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 14 August 1984

Accepted 01 January 1985

Publication Date:
18 July 2018 (online)

  PDF Download  Permissions and Reprints

Summary

Previously, we demonstrated that in vivo regulation of liver fibrinogen synthesis occurs via the fibrinogen mRNA level. However, the molecular regulatory mechanism of fibrinogen synthesis is still not well understood. Fibrinogen or fibrin degradation products might play an important role in regulating fibrinogen synthesis. In our present study, we have injected rats intraperitoneally with purified homologous fragments and measured the liver content of mRNA specific coding for fibrinogen. Increased levels of fibrinogen mRNA and elevated plasma fibrinogen concentrations were observed in rats after administration of fibrinogen degradation products X, Y, DEGTA Dcate or E. Fragment E or E’ has a less stimulatory effect than X, Y or Dcate, whereas cross-linked fibrin degradation product D dimer does not increase fibrinogen synthesis. This article reports for the first time a stimulatory effect of the high molecular weight fibrinogen degradation products on fibrinogen synthesis.

Keywords

Fibrinogen mRNA - Fibrinogen synthesis - Fibrinogen fragments - Fibrin degradation products - Isolated hepatocytes
 

  • References

  • 1 Koj A. Acute phase reactants: their synthesis, turnover and biological significance. In Allison AC. (Ed) Structure and function of plasma proteins. Plenum Press; New York: 1974. pp 73-131
    Google Scholar
  • 2 Princen JM G, Nieuwenhuizen W, Mol-Backx GP B M, Yap SH. Direct evidence of transcriptional control of fibrinogen and albumin synthesis in rat liver during the acute phase response. Biochem Biophys Res Commun 1981; 102: 717-723
    CrossrefPubMedGoogle Scholar
  • 3 Princen HM G, Selten GC M, Selten-Versteegen AE, Mol-Backx GP B M, Nieuwenhuizen W, Yap SH. Distribution of mRNAs of fibrinogen polypeptides and albumin in free and membrane-bound polyribosomes and induction of α-fetoprotein mRNA synthesis during liver regeneration after partial hepatectomy. Biochim Biophys Acta 1982; 699: 121-130
    CrossrefPubMedGoogle Scholar
  • 4 Crane LJ, Miller DL. Plasma protein synthesis by isolated rat hepatocytes. J Cell Biol 1977; 72: 11-25
    CrossrefPubMedGoogle Scholar
  • 5 Grieninger G, Plant PW, Liang TJ, Kalb RG, Amrani D, Mosesson MW, Hertzberg KM, Pindyck J. Hormonal regulation of fibrinogen synthesis in cultured hepatocytes. Ann NY Acad Sci 1983; 408: 469-489
    CrossrefPubMedGoogle Scholar
  • 6 Princen HM G, Moshage HJ, de Haard HJ W, van Gemert PJ L, Yap SH. The influence of glucocorticoid on the fibrinogen messenger RNA content of rat liver in vivo and in hepatocyte suspension culture. Biochem J 1984; 220: 631-637
    CrossrefPubMedGoogle Scholar
  • 7 Pickart LR, Thaler MM. Free fatty acids and albumin as mediator of thrombin-stimulated fibrinogen synthesis. Am J Physiol 1976; 230: 996-1002
    PubMedGoogle Scholar
  • 8 Kampschmidt RF, Upchurch HF, Pulliam LA. Characterization of a leukocyte-derived endogenous mediator responsible for increased plasma fibrinogen. Ann NY Acad Sci 1982; 389: 338-353
    CrossrefPubMedGoogle Scholar
  • 9 Ritchie DG, Levy BA, Adams MA, Fuller GM. Regulation of fibrinogen synthesis by plasmin-derived fragment of fibrinogen and fibrin: An indirect feedback pathway. Proc Natl Acad Sci USA 1982; 79: 1530-1534
    CrossrefPubMedGoogle Scholar
  • 10 Barnhart MY, Cress DC, Noonan SM, Walsh RT. Influence of fibrinolytic products on hepatic release and synthesis of fibrinogen. Thrombos Diathes Haemorrh 1970; 39 (Suppl) 143-159
    PubMedGoogle Scholar
  • 11 Kessler CM, Bell WR. The effect of homologous thrombin and fibrinogen degradation products on fibrinogen synthesis in rabbits. J Lab Clin Med 1979; 93: 768-782
    PubMedGoogle Scholar
  • 12 Ittyerah TR, Weidner N, Wochner RD, Sherman LA. Effect of fibrin degradation products and thrombin on fibrinogen synthesis. Br J Haematol 1979; 43: 661-668
    CrossrefPubMedGoogle Scholar
  • 13 Otis PT, Rapaport SJ. Failure of fibrinogen degradation products to increase plasma fibrinogen in rabbits. Proc Soc Exp Biol Med 1973; 144: 124-129
    CrossrefPubMedGoogle Scholar
  • 14 Kessler CM, Bell WR. Regulation of fibrinogen biosynthesis: effect of fibrin degradation products, low-molecular-weight peptides of fibrinogenolysis and fibrinopeptides A and B. J Lab Clin Med 1979; 93: 758-767
    PubMedGoogle Scholar
  • 15 Bocci V, Conti T, Muscettola M, Pacini A, Pessina GP. Factors regulating plasma protein synthesis. IV Influence of fragments D and E on plasma fibrinogen concentration. Thrombos Diathes Haemorrh 1974; 31: 395-402
    PubMedGoogle Scholar
  • 16 Franks JJ, Kirsch RE, Frith LO C, Purves LR, Franks WT, Franks JA, Mason P, Saunders SJ. Effect of fibrinogenolytic products D and E on fibrinogen and albumin synthesis in the rat. J Clin Invest 1981; 67: 575-580
    CrossrefPubMedGoogle Scholar
  • 17 Bell WR, Kessler CM, Townsend RR. Stimulation of fibrinogen biosynthesis by fibrinogen fragments D and E. Br J Haematol 1983; 53: 599-610
    CrossrefPubMedGoogle Scholar
  • 18 Kessler CM, Bell WR. Stimulation of fibrinogen synthesis: A possible functional role of fibrinogen degradation products. Blood 1980; 55: 40-47
    PubMedGoogle Scholar
  • 19 van Ruyven-VermeerY A M, Nieuwenhuizen W. Purification of rat fibrinogen and its constituent chains. Biochem J 1978; 169: 653-658
    CrossrefPubMedGoogle Scholar
  • 20 Nieuwenhuizen W, Gravesen M. Anticoagulant and calcium-binding properties of high molecular weight derivatives of human fibrinogen, produced by plasmin (fragments X). Biochim Biophys Acta 1981; 669: 81-88
    PubMedGoogle Scholar
  • 21 Nieuwenhuizen W, Voskuilen M, Hermans J. Anticoagulant and calcium-binding properties of high molecular weight derivatives of human fibrinogen (plasmin-fragments Y). Biochim Biophys Acta 1982; 708: 313-316
    CrossrefPubMedGoogle Scholar
  • 22 van Ruyven-VermeerY A M, Nieuwenhuizen W, Haverkate F, Timan T. A novel method for the rapid purification of human and rat fibrin(ogen) degradation products in high yields. Hoppe-Seyler’s Z Physiol Chem 1979; 360: 633-637
    PubMedGoogle Scholar
  • 23 Levin J, Bang FB. Clottable protein in Limulus: Its localization and kinetics of its coagulation by endotoxin. Thrombos Diathes Haemorrh 1968; 19: 186-197
    PubMedGoogle Scholar
  • 24 Strair RK, Yap SH, Shafritz DA. Use of molecular hybridization to purify and analyze albumin messenger RNA from rat liver. Proc Natl Acad Sci USA 1977; 74: 4346-4350
    CrossrefPubMedGoogle Scholar
  • 25 Taylor JM, Schimke RT. Synthesis of rat liver albumin in a rabbit reticulocyte cell-free protein-synthesizing system. J Biol Chem 1973; 248: 7761-7768
    PubMedGoogle Scholar
  • 26 Housman D, Skoultchi A, Forget BG, Benz EJ. Use of globin cDNA as a hybridization probe for globin mRNA. Ann NY Acad Sci 1979; 241: 280-289
    PubMedGoogle Scholar
  • 27 Selten GC M, Princen HM G, Selten-Versteegen AE, Mol-Backx GP B M, Yap SH. Sequence content of α-fetoprotein, albumin and fibrinogen polypeptide mRNAs in different organs, developing tissues and in liver during carcinogenesis in rats. Biochim Biophys Acta 1982; 699: 131-137
    CrossrefPubMedGoogle Scholar
  • 28 Fleck A, Munro HN. The precision of ultraviolet absorption measurements in the Schmidt-Thannhauser procedure for nucleic acid estimation. Biochim Biophys Acta 1962; 55: 571-583
    CrossrefPubMedGoogle Scholar
  • 29 Weber K, Osborn M. The reliability of molecular weight determinations by dodecyl-sulfate-polyacrylamide gel electrophoresis. J Biol Chem 1969; 244: 4406-4412
    PubMedGoogle Scholar
  • 30 Vermylen C, de Vreeker R, Verstraete M. A rapid enzymatic method for assay of fibrinogen fibrin polymerization time (FPT test). Clin Chim Acta 1963; 8: 418-423
    CrossrefPubMedGoogle Scholar
  • 31 Princen HM G, Selten GC M, Nieuwenhuizen W, Yap SH. Changes of synthesis of fibrinopeptide and albumin mRNAs in rat liver after turpentine injection and after partial hepatectomy or laparatomy. In Haverkate F, Henschen A, Nieuwenhuizen W, Straub PW. (Eds) Fibrinogen-structure, Functional aspects Metabolism. Walter de Gruyter & Co; Berlin: 1983. 2 48-62
    Google Scholar
  • 32 Pickart LR, Pilgeram LO. The role of thrombin in fibrinogen biosynthesis. Thrombos Diathes Haemorrh 1967; 17: 358-364
    PubMedGoogle Scholar
  • 33 Graves CM, Munns TW, Carlisle TL, Grant GA, Strauss AW. Induction of prothrombin synthesis by prothrombin fragments. Proc Natl Acad Sci USA 1982; 78: 4772-4776
    PubMedGoogle Scholar