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. 2000 Mar 15;346(Pt 3):603–610.

Hepatic expression, synthesis and secretion of a novel fibrinogen/angiopoietin-related protein that prevents endothelial-cell apoptosis.

I Kim 1, H G Kim 1, H Kim 1, H H Kim 1, S K Park 1, C S Uhm 1, Z H Lee 1, G Y Koh 1
PMCID: PMC1220891  PMID: 10698685

Abstract

Using degenerate PCR we isolated a cDNA encoding a novel 406- and 410-amino acid protein from human and mouse embryonic cDNAs and have designated it 'hepatic fibrinogen/angiopoietin-related protein' (HFARP). The N-terminal and C-terminal portions of HFARP contain the characteristic coiled-coil domains and fibrinogen-like domains that are conserved in angiopoietins. In human and mouse tissues, HFARP mRNA is specifically expressed in the liver. HFARP mRNA and protein are mainly present in the hepatocytes. HFARP has a highly hydrophobic region at the N-terminus that is typical of a secretory signal sequence and one consensus glycosylation site. Recombinant HFARP expressed in COS-7 cells is secreted and glycosylated. HFARP protein is present not only in the hepatocytes, but also in the circulating blood. Recombinant HFARP acts as an apoptosis survival factor for vascular endothelial cells, but does not bind to Tie1 or Tie2 (endothelial-cell tyrosine kinase receptors). These results suggest that HFARP may exert a protective function on endothelial cells through an endocrine action.

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Selected References

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  1. Baumann R. E., Henschen A. H. Human fibrinogen polymorphic site analysis by restriction endonuclease digestion and allele-specific polymerase chain reaction amplification: identification of polymorphisms at positions A alpha 312 and B beta 448. Blood. 1993 Oct 1;82(7):2117–2124. [PubMed] [Google Scholar]
  2. Brown W. M., Dziegielewska K. M., Foreman R. C., Saunders N. R. Nucleotide and deduced amino acid sequence of a gamma subunit of bovine fibrinogen. Nucleic Acids Res. 1989 Aug 11;17(15):6397–6397. doi: 10.1093/nar/17.15.6397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Davis S., Aldrich T. H., Jones P. F., Acheson A., Compton D. L., Jain V., Ryan T. E., Bruno J., Radziejewski C., Maisonpierre P. C. Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning. Cell. 1996 Dec 27;87(7):1161–1169. doi: 10.1016/s0092-8674(00)81812-7. [DOI] [PubMed] [Google Scholar]
  4. Holash J., Maisonpierre P. C., Compton D., Boland P., Alexander C. R., Zagzag D., Yancopoulos G. D., Wiegand S. J. Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science. 1999 Jun 18;284(5422):1994–1998. doi: 10.1126/science.284.5422.1994. [DOI] [PubMed] [Google Scholar]
  5. Ichijo H., Hellman U., Wernstedt C., Gonez L. J., Claesson-Welsh L., Heldin C. H., Miyazono K. Molecular cloning and characterization of ficolin, a multimeric protein with fibrinogen- and collagen-like domains. J Biol Chem. 1993 Jul 5;268(19):14505–14513. [PubMed] [Google Scholar]
  6. Kang M. J., Koh G. Y. Differential and dramatic changes of cyclin-dependent kinase activities in cardiomyocytes during the neonatal period. J Mol Cell Cardiol. 1997 Jul;29(7):1767–1777. doi: 10.1006/jmcc.1997.0450. [DOI] [PubMed] [Google Scholar]
  7. Kim H., Ko J. P., Kang U. G., Park J. B., Kim H. L., Lee Y. H., Kim Y. S. Electroconvulsive shock reduces inositol 1,4,5-trisphosphate 3-kinase mRNA expression in rat dentate gyrus. J Neurochem. 1994 Nov;63(5):1991–1994. doi: 10.1046/j.1471-4159.1994.63051991.x. [DOI] [PubMed] [Google Scholar]
  8. Kim I., Moon S. O., Koh K. N., Kim H., Uhm C. S., Kwak H. J., Kim N. G., Koh G. Y. Molecular cloning, expression, and characterization of angiopoietin-related protein. angiopoietin-related protein induces endothelial cell sprouting. J Biol Chem. 1999 Sep 10;274(37):26523–26528. doi: 10.1074/jbc.274.37.26523. [DOI] [PubMed] [Google Scholar]
  9. Koblizek T. I., Weiss C., Yancopoulos G. D., Deutsch U., Risau W. Angiopoietin-1 induces sprouting angiogenesis in vitro. Curr Biol. 1998 Apr 23;8(9):529–532. doi: 10.1016/s0960-9822(98)70205-2. [DOI] [PubMed] [Google Scholar]
  10. Kwak H. J., So J. N., Lee S. J., Kim I., Koh G. Y. Angiopoietin-1 is an apoptosis survival factor for endothelial cells. FEBS Lett. 1999 Apr 9;448(2-3):249–253. doi: 10.1016/s0014-5793(99)00378-6. [DOI] [PubMed] [Google Scholar]
  11. Kyte J., Doolittle R. F. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. doi: 10.1016/0022-2836(82)90515-0. [DOI] [PubMed] [Google Scholar]
  12. Maisonpierre P. C., Suri C., Jones P. F., Bartunkova S., Wiegand S. J., Radziejewski C., Compton D., McClain J., Aldrich T. H., Papadopoulos N. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science. 1997 Jul 4;277(5322):55–60. doi: 10.1126/science.277.5322.55. [DOI] [PubMed] [Google Scholar]
  13. Mustonen T., Alitalo K. Endothelial receptor tyrosine kinases involved in angiogenesis. J Cell Biol. 1995 May;129(4):895–898. doi: 10.1083/jcb.129.4.895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Nehls V., Drenckhahn D. A microcarrier-based cocultivation system for the investigation of factors and cells involved in angiogenesis in three-dimensional fibrin matrices in vitro. Histochem Cell Biol. 1995 Dec;104(6):459–466. doi: 10.1007/BF01464336. [DOI] [PubMed] [Google Scholar]
  15. Papapetropoulos A., García-Cardeña G., Dengler T. J., Maisonpierre P. C., Yancopoulos G. D., Sessa W. C. Direct actions of angiopoietin-1 on human endothelium: evidence for network stabilization, cell survival, and interaction with other angiogenic growth factors. Lab Invest. 1999 Feb;79(2):213–223. [PubMed] [Google Scholar]
  16. Partanen J., Armstrong E., Mäkelä T. P., Korhonen J., Sandberg M., Renkonen R., Knuutila S., Huebner K., Alitalo K. A novel endothelial cell surface receptor tyrosine kinase with extracellular epidermal growth factor homology domains. Mol Cell Biol. 1992 Apr;12(4):1698–1707. doi: 10.1128/mcb.12.4.1698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Peek R., van Gelderen B. E., Bruinenberg M., Kijlstra A. Molecular cloning of a new angiopoietinlike factor from the human cornea. Invest Ophthalmol Vis Sci. 1998 Sep;39(10):1782–1788. [PubMed] [Google Scholar]
  18. Pober J. S., Cotran R. S. Cytokines and endothelial cell biology. Physiol Rev. 1990 Apr;70(2):427–451. doi: 10.1152/physrev.1990.70.2.427. [DOI] [PubMed] [Google Scholar]
  19. Puri M. C., Rossant J., Alitalo K., Bernstein A., Partanen J. The receptor tyrosine kinase TIE is required for integrity and survival of vascular endothelial cells. EMBO J. 1995 Dec 1;14(23):5884–5891. doi: 10.1002/j.1460-2075.1995.tb00276.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rehwald M., Neuschäfer-Rube F., de Vries C., Püschel G. P. Possible role for ligand binding of histidine 81 in the second transmembrane domain of the rat prostaglandin F2alpha receptor. FEBS Lett. 1999 Jan 29;443(3):357–362. doi: 10.1016/s0014-5793(99)00007-1. [DOI] [PubMed] [Google Scholar]
  21. Sato T. N., Tozawa Y., Deutsch U., Wolburg-Buchholz K., Fujiwara Y., Gendron-Maguire M., Gridley T., Wolburg H., Risau W., Qin Y. Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation. Nature. 1995 Jul 6;376(6535):70–74. doi: 10.1038/376070a0. [DOI] [PubMed] [Google Scholar]
  22. Suri C., Jones P. F., Patan S., Bartunkova S., Maisonpierre P. C., Davis S., Sato T. N., Yancopoulos G. D. Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell. 1996 Dec 27;87(7):1171–1180. doi: 10.1016/s0092-8674(00)81813-9. [DOI] [PubMed] [Google Scholar]
  23. Valenzuela D. M., Griffiths J. A., Rojas J., Aldrich T. H., Jones P. F., Zhou H., McClain J., Copeland N. G., Gilbert D. J., Jenkins N. A. Angiopoietins 3 and 4: diverging gene counterparts in mice and humans. Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):1904–1909. doi: 10.1073/pnas.96.5.1904. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Yamamoto T., Gotoh M., Sasaki H., Terada M., Kitajima M., Hirohashi S. Molecular cloning and initial characterization of a novel fibrinogen-related gene, HFREP-1. Biochem Biophys Res Commun. 1993 Jun 15;193(2):681–687. doi: 10.1006/bbrc.1993.1678. [DOI] [PubMed] [Google Scholar]
  25. Ziegler S. F., Bird T. A., Schneringer J. A., Schooley K. A., Baum P. R. Molecular cloning and characterization of a novel receptor protein tyrosine kinase from human placenta. Oncogene. 1993 Mar;8(3):663–670. [PubMed] [Google Scholar]
  26. von Heijne G. A new method for predicting signal sequence cleavage sites. Nucleic Acids Res. 1986 Jun 11;14(11):4683–4690. doi: 10.1093/nar/14.11.4683. [DOI] [PMC free article] [PubMed] [Google Scholar]

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