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

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.

Fat poetry: a kingdom for PPARγ

“…It is noteworthy that the proband, when treated with pharmacological doses of www.cell-research.com | Cell Research Silvia I Anghel and Walter Wahli 501 npg rosiglitazone, in combination with metformin, had a good glycemic control [193]. Another well-studied variant is the PPARg 2 P12A [70,73,194,195]. This is the only well-described change found so far in the N-terminal domain of PPARg 2 .…”

“…This is the only well-described change found so far in the N-terminal domain of PPARg 2 . The initial study of Finnish and second-generation Japanese populations concluded that the less common 12A allele promotes insulin sensitivity and confers protection against type 2 diabetes [70,73,194,195]. In vitro studies showed that this allele reduces PPARg DNA binding affinity and transcriptional activity [70,73,194,195].…”

“…Angiopoietin-like proteins (ANGPTLs) are also involved in the regulation of energy homeostasis [69]. One of them, the fasting-induced adipose factor (FIAF), also called ANGPTL4, HFARP and PGAR [70][71][72][73], is most highly expressed in the adipose tissue and secreted into the circulation, where it is found associated with plasma lipoproteins. Adenovirus-mediated overexpression of FIAF was found to improve hyperinsulinemia, hyperglycemia and glucose tolerance [74].…”

“…The initial study of Finnish and second-generation Japanese populations concluded that the less common 12A allele promotes insulin sensitivity and confers protection against type 2 diabetes [70,73,194,195]. In vitro studies showed that this allele reduces PPARg DNA binding affinity and transcriptional activity [70,73,194,195]. Although some additional studies did not support a statistically significant role for the PPARg 2 P12A polymorphism in the etiology of type 2 diabetes [196][197][198], a more recent meta-analysis of all published data, comprising more than 25 000 cases of diabetes, showed an association of P12A with type 2 diabetes [199].…”

Association between angiopoietin-like 6 (ANGPTL6) gene polymorphisms and metabolic syndrome-related phenotypes in the French MONICA Study

“…Angiopoietin-like proteins [ANGPTLs] or 'angiopoietinrelated proteins' [ARPs] are orphan ligands with a degree of similarity to angiopoietins: they contain a coiled-coil domain and a fibrinogen-like domain, and have angiogenic effects [1][2][3][4][5][6][7][8][9][10]. The ANGPTL family has seven members (ANGPTL 1-7), which have been found in both humans and mice [11] (except for ANGPTL5, identified only in humans [12]).…”