Disease relevance of Serpinf1

• PEDF expression was higher in the less angiogenic C57BL/6J strain at 6, 12, 24, and 96 h hypoxia (P < 0.03), while TSP-1 expression was higher in C57BL/6J throughout the entire time course of hypoxia (4 days) compared to 129S3/SvIM (P < 0.02) [1].
• These findings suggest that caspin/pigment epithelium-derived factor/early population doubling level cDNA-1 is a novel factor that might play a crucial role in embryogenesis and tumor metastasis through binding to the extracellular matrix [2].
• Isolation, purification, and characterization of a collagen-associated serpin, caspin, produced by murine colon adenocarcinoma cells [2].
• Caspin also demonstrated high homology with human pigment epithelium-derived factor/early population doubling level cDNA-1, which reportedly induces neuronal differentiation of human retinoblastoma cells and is expressed in association with G0 growth arrest [2].
• We previously reported the loss of PEDF expression in glioma progression [3].

High impact information on Serpinf1

• Pigment epithelium-derived factor regulates the vasculature and mass of the prostate and pancreas [4].
• In vivo, androgen ablation increased PEDF in normal rat prostates and in human cancer biopsies [4].
• Androgens inhibited prostatic PEDF expression in cultured cells [4].
• Inducer-stimulated Fas targets activated endothelium for destruction by anti-angiogenic thrombospondin-1 and pigment epithelium-derived factor [5].
• Here we show that two such inhibitors, thrombospondin-1 and pigment epithelium-derived factor, derive specificity for remodeling vessels from their dependence on Fas/Fas ligand (FasL)-mediated apoptosis to block angiogenesis [5].

Chemical compound and disease context of Serpinf1

• Dexamethasone was also effective at increasing PEDF RNA levels in both mouse Muller glial cells and C6 rat glioma cells [6].

Biological context of Serpinf1

• We now describe the localization of PEDF in regions of active bone formation in the mid-gestation mouse embryo and its specific and high levels of secretion by osteoblasts [7].
• To address this therapeutic gap, we determined the efficacy of recombinant adeno-associated viral (rAAV) serotype-2-mediated expression of pigment epithelium-derived factor (PEDF) or Kringle domains 1-3 of angiostatin (K1K3) in reducing aberrant vessel formation in a mouse model of ischemia-induced retinal NV [8].
• However, the signal-transduction pathways regulated by PEDF remain to be elucidated [9].
• However, when early-passage fibroblasts are made quiescent by both serum deprivation and density-dependent contact inhibition and then stimulated with serum, steady-state EPC-1 transcript levels remain relatively constant throughout a 36 h period following serum stimulation [10].
• We have characterized the EPC-1 transcript with respect to its cell-cycle regulation, tissue specificity, and interspecies conservation of related genomic sequences [10].

Anatomical context of Serpinf1

• Periocular delivery of an adenoviral vector encoding pigment epithelium-derived factor (PEDF), another secreted protein, resulted in high levels of PEDF in the retinal pigmented epithelium and choroid, but not in the retina [11].
• Vitamin A up-regulates the expression of thrombospondin-1 and pigment epithelium-derived factor in retinal pigment epithelial cells [12].
• PEDF is detected to a lesser extent in osteoclasts as well [7].
• Pigment epithelial derived factor (PEDF) is one of the most effective inhibitors of angiogenesis described so far, especially in controlling the growth of blood vessels in the eye [7].
• The number of such vascular endothelial cell nuclei in eyes treated with rAAV-PEDF or rAAV-K1K3 was significantly reduced (both P < 0.0000002) compared with control eyes [8].

Associations of Serpinf1 with chemical compounds

• By utilizing residue-specific chemical modification and site-directed mutagenesis techniques, we revealed that the acidic amino acid residues on PEDF (Asp(255), Asp(257), and Asp(299)) are critical to collagen binding, and three clustered basic amino acid residues (Arg(145), Lys(146), and Arg(148)) are necessary for heparin binding [13].
• It will be an interesting therapeutic strategy to co-administer PEDF and retinoic acid in developing protocols for neovascular diseases in the eye and in cancer [6].
• Plasmids containing a PEDF promoter regulating a luciferase gene were transfected into D407 and C6 cells and the luciferase activity measured after incubation in the presence or absence of ATRA [6].
• PURPOSE: Pigment epithelium-derived factor (PEDF), a neurotrophic protein, is a member of the serine protease inhibitor supergene family [14].
• Retinoic acid and dexamethasone regulate the expression of PEDF in retinal and endothelial cells [6].

Other interactions of Serpinf1

• Osteoblasts and osteoclasts express PEDF, VEGF-A isoforms, and VEGF receptors: possible mediators of angiogenesis and matrix remodeling in the bone [7].
• Pigment epithelium-derived factor (PEDF) was increased more than 67-fold compared to Ang-2 in resting cornea of both C57BL/6J and 129S3/SvIM strains (P < 0.0001; P < 0.0001), suggesting a strongly antiangiogenic environment [15].
• Mapping of these residues on the crystal structure of human PEDF (Simonovic, M., Gettins, P. G. W., and Volz, K. (2001) Proc. Natl. Acad. Sci. U.S.A. 98, 11131-11135) demonstrated that the collagen-binding site is oriented toward the opposite side of the highly basic surface where the heparin-binding site is localized [13].
• Here, we identify the angiogenesis inhibitor pigment epithelium-derived factor (PEDF) as a key inhibitor of stromal vasculature and epithelial tissue growth in mouse prostate and pancreas [4].
• PURPOSE: Pigment Epithelium-Derived Factor (PEDF) is a 50 kDa secretable protein with neuroprotective, neurotrophic, and antiangiogenic properties [16].

Analytical, diagnostic and therapeutic context of Serpinf1

• Indirect ELISA was used to correlate VEGF and PEDF protein levels with mRNA expression [1].
• In this study, we analysed the expression pattern of PEDF in growing mouse hindlimbs from newborn day one through to maturation at week 9, using immunohistochemistry and in situ hybridization [17].
• To test the effects of PEDF on retinoic acid function, expression of retinoic acid receptors in Y-79 and A-RPE 19 cells was measured by PCR [6].
• Northern blot analysis shows the presence of the PEDF transcript in a broad range of adult mouse tissues with liver showing the highest level of expression [14].
• Southern blot analysis indicates that the mouse genome contains only one gene for PEDF [14].

References