Disease relevance of FGL2

• Fibrinogen-like protein 2 fibroleukin expression and its correlation with disease progression in murine hepatitis virus type 3-induced fulminant hepatitis and in patients with severe viral hepatitis B [1].
• AIM: To evaluate the expression of fibrinogen-like protein 2 (fgl2) and its correlation with disease progression in both mice and patients with severe viral hepatitis [1].
• Collectively, the results of this study define both viral and host factors necessary for induction of fgl2 prothrombinase gene transcription in MHV infection and may provide an explanation for the hepatotrophic nature of MHV-induced fulminant hepatic failure [2].
• Purified fgl2 protein generated in a baculovirus expression system had no measurable prothrombinase activity, whereas the activity was restored when the purified protein was reconstituted into phosphatidyl-L-serine-containing vesicles [3].
• We have reported recently that the nucleocapsid (N) protein from strains of murine hepatitis virus (MHV-3, MHV-A59), which cause massive hepatocellular necrosis but not from strains (MHV-JHM, MHV-2) which do not produce serious liver disease, induces transcription of fgl2 [2].

High impact information on FGL2

• One of these genes, represented by the cDNA clone pT49, is expressed in cytotoxic T lymphocytes but not in helper T lymphocytes or B lymphocytes [4].
• In spite of the strong homology of pT49 protein to the fibrinogen subunits, the positions of the introns in the pT49 gene are totally different from those of the fibrinogen genes [4].
• Human fgl2 mRNA transcripts and protein were markedly expressed mainly in renal tubule cells, infiltrating lymphoid cells including macrophages, CD8(+) T cells, mature B cells (plasma cells), and endothelial cells [5].
• Dual staining showed fibrin deposition was localized mainly to blood vessels, in the glomerulus and interstitium and the lumen of tubules, and occurred in association with human fgl2 expression [5].
• Treatment of wild-type mice with a neutralizing anti-fgl2 Ab ameliorated histological evidence for allorejection and intravascular fibrin deposition, and resulted in an increase in graft survival [5].

Chemical compound and disease context of FGL2

• Increased fgl2 prothrombinase activity in maternal decidua and fetal trophoblasts may trigger abortions by proinflammatory cytokines induced by bacterial lipopolysaccharide (LPS) in mice and is implicated in human recurrent miscarriages and pre-eclampsia [6].

Biological context of FGL2

• The FGL2 gene is a single-copy gene in the haploid human genome and has two exons separated by a 2195-bp intron expressing two mRNA transcripts of 1.5 and 5.0 kb [7].
• Both HFGL2 and FGL2 encode a type II transmembrane protein with a predicted catalytic domain toward the amino terminus of the protein [8].
• FGL2 prothrombinase expression may mediate the role of thrombin in human parturition [9].
• We used a murine pT49 probe to screen a human small intestine cDNA library, and obtained a set of overlapping cDNA clones encoding a Fib-like protein that is 80% identical with the product of the murine pT49 gene [10].
• Novel mfgl2 antisense plasmid inhibits murine fgl2 expression and ameliorates murine hepatitis virus type 3-induced fulminant hepatitis in BALB/cJ mice [11].

Anatomical context of FGL2

• CONCLUSION: The expression of FGL2 messenger RNA is increased in gravid myometrium compared with nonpregnant samples [9].
• Region-specific expression and secretion of the fibrinogen-related protein, fgl2, by epithelial cells of the hamster epididymis and its role in disposal of defective spermatozoa [12].
• Immunoelectron microscopy revealed that fgl2 was distributed throughout an amorphous, "death cocoon," complex assembled onto abnormal spermatozoa and that the smaller fgl2 aggregates consisted of the amorphous material with embedded sperm fragments, organelles, and membrane vesicles [12].
• A comprehensive assessment of basal fgl2 promoter activity in murine vascular endothelial cells defined a minimal 119 bp region responsible for constitutive fgl2 transcription [13].
• Constitutive expression of fgl2 transcripts at low levels are seen in cytotoxic T cells, endothelial, intestinal and trophoblast cells, while specific factors (such as virus and cytokines) are required to induce high levels of fgl2 expression in other cell types including monocytes/macrophages [13].

Associations of FGL2 with chemical compounds

• Significantly higher levels of FGL2 expression were found in the gravid women compared with the women who were treated with misoprostol (P <.001), the premenopausal nonpregnant women (P <.001), and the menopausal women (P <.0001) [9].
• The purpose of this study was to determine FGL2 messenger RNA expression in human myometrium and to assess its relationship to the expression of EP3-6 prostaglandin receptor and inducible nitric oxide synthase [9].
• In this work we provide direct evidence that fgl2 cleaves prothrombin to thrombin consistent with serine protease activity and requires calcium, phospholipids, and factor Va for its full activity [3].
• Furthermore, fgl2 prothrombinase activity was not inhibited by antithrombin III, soybean trypsin inhibitor, 4-aminobenzamidine, aprotinin, or phenylmethylsulfonyl fluoride, whereas diisopropylfluorophosphate completely abrogated the activity [3].
• The fgl2 prothrombinase/fibroleukin gene is required for lipopolysaccharide-triggered abortions and for normal mouse reproduction [6].

Other interactions of FGL2

• FGL2 messenger RNA expression was determined with the use of semiquantitative polymerase chain reaction and was compared with previously determined messenger RNA expression levels for EP3-6 and inducible nitric oxide synthase for the same samples [9].
• Conversely, a group of genes, including fibrinogen-like protein 2 and legumain, were expressed at a higher level in macrophages infected with WAg520 compared to ATCC35723 [14].

Analytical, diagnostic and therapeutic context of FGL2

• By both radiation hybrid analyses and fluorescence in situ hybridization, human FGL2 was localized to 7q11.23 [7].
• Role of fibrinogen-like protein 2 prothrombinase/fibroleukin in experimental and human allograft rejection [5].
• To address further the relevance of fgl2 in acute allograft rejection, we examined kidney biopsies from patients who had undergone renal transplantation [5].
• A polyclonal antibody against fgl2 was used to detect the expression of both mouse and human fgl2 protein in liver samples as well as in PBMC by immunohistochemistry staining in a separate set of studies [1].
• SDS-PAGE and microsequence analyses revealed that the Mr 64,000 fgl2 monomer was assembled into two disulfide-linked oligomers of Mr 260,000 and 280,000 [12].

References