Biochem. J. (2000) 346
(603–610) (Printed in Great Britain)
Hepatic expression, synthesis and secretion of a novel fibrinogen/angiopoietin-related protein that prevents endothelial-cell apoptosis
Injune KIM*, Hwan-Gyu KIM*, Hyun KIM‡, Hong-Hee KIM§, Sung Kwang PARK†, Chang-Sub UHM‡, Zang Hee LEE§ and Gou Young KOH*1
*National Creative Research Initiatives Center for Cardiac Regeneration and Institute of Cardiovascular Research, Chonbuk National University School of Medicine, Chonju, 560-180, Korea, †Department of Internal Medicine, Chonbuk National University School of Medicine, Chonju, 560-180, Korea, ‡Department of Anatomy, Institute of Human Genetics and Graduate School of Biotechnology, Korea University, Seoul, 136-705, Korea, and §Department of Microbiology and Immunology, Chosun University Dental School, Kwangju, 501-759, Korea
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.
Abbreviations used: HFARP, hepatic fibrinogen/angiopoietin-related protein; Ang, angiopoietin; ARP, angiopoietin-related protein; RACE, rapid amplification of cDNA ends; HUVECs, human umbilical-vein endothelial cells; PPAECs, porcine pulmonary arterial endothelial cells; E, embryonic day; CMV, cytomegalovirus; VEGF
165, vascular endothelial growth factor
165; TUNEL, terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling; hFREP-1, human fibrinogen-related protein 1; pFicloinB, porcine ficolin
b; hpFGA, human fibrinogen A polypeptide; PNGase-F, peptide N-glycosidase F; MC, microcarrier.
1 To whom correspondence should be addressed (e-mail gykoh@moak.chonbuk.ac.kr).
The nucleotide sequences for the human and mouse hepatic angiopoietin-related protein genes have been deposited in the GenBank®, DDBJ and EMBL Nucleotide Sequence Databases under the accession numbers AF169312 and AF169313.
Key words: endocrine; liver; Tie receptor.
Received 11 November 1999; accepted 4 January 2000
The Biochemical Society, London © 2000
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