The reference OMIM entry for this protein is 172860

Serpin peptidase inhibitor, clade f, member 1; serpinf1
Pigment epithelium-derived factor; pedf

DESCRIPTION

The SERPINF1 gene is a member of the serpin gene family. Serpins are a group of serine protease inhibitors, some of which have also been reported to exhibit neurotrophic activity.

MAPPING

By the analysis of 3 independent somatic cell hybrid panels, Tombran-Tink et al. (1994) assigned the PEDF gene to chromosome 17. Fluorescence in situ hybridization showed localization at the terminal portion of 17p. PCR analysis of somatic cell hybrids containing specific regions of 17 were subsequently used to sublocalize PEDF to 17pter-p13.1. Greenberg et al. (1997) used linkage analysis to narrow the localization of the PEDF gene to 17p13.3, the same region as that carrying the autosomal dominant retinitis pigmentosa locus (RP13; 600059) identified in a South African family.

GENE FUNCTION

Pigment epithelium-derived factor, originally identified in conditioned medium of cultured human fetal retinal pigment epithelial (RPE) cells, induces extensive neuronal differentiation in human Y79 retinoblastoma cells, a neoplastic counterpart of normal retinoblasts. Steele et al. (1993) suggested that PEDF is synthesized by RPE cells and secreted into the retina interphotoreceptor matrix where it may influence development/differentiation of the neural retina. In studies aimed at identifying antiangiogenic factors in the eye, Dawson et al. (1999) identified PEDF. Biochemically purified as well as recombinant forms of PEDF potently inhibited neovascularization in the rat cornea. In vitro, PEDF inhibited endothelial cell migration in a dose-dependent manner with a median effective dose of 0.4 nanomolar, placing it among the most potent natural inhibitors of angiogenesis in this assay, slightly more active than pure angiostatin (see 173350), thrombospondin I (188060), and endostatin (see 120328). At doses of 1.0 nanomolar or greater, PEDF also inhibited basic fibroblast growth factor (see 131220)-induced proliferation of capillary endothelial cells by 40%. The amount of inhibitory PEDF produced by retinal cells was positively correlated with oxygen concentrations, suggesting that its loss plays a permissive role in ischemia-driven retinal neovascularization. These results suggested that PEDF may be of therapeutic use, especially in retinopathies where pathologic neovascularization compromises vision and leads to blindness. PEDF may also prove to be a useful therapeutic for retinoblastomas, where its dual activities in reducing cell differentiation and inhibiting angiogenesis may be particularly effective. King and Suzuma (2000) reviewed the role of pigment epithelium-derived factor as a key coordinator of retinal neuronal and vascular functions. Aymerich et al. (2001) examined native neural retinas from adult steers for the expression of PEDF receptors and conclusively demonstrated the existence of PEDF receptors discretely distributed on the surface of cells from the adult retinal cells. They suggested that the results also provided evidence for the direct action of PEDF on photoreceptor and ganglion cell neurons and an anatomic basis for studies to assess PEDF neurotrophic effects on the adult retina. Simonovic et al. (2001) pointed out that PEDF is the most potent inhibitor of angiogenesis in the mammalian ocular compartment. It also has neurotrophic activity, both in the retina and in the central nervous system, and is highly upregulated in young versus senescent fibroblasts. To provide a structural basis for understa ... More on the omim web site

Subscribe to this protein entry history

Feb. 23, 2019: Protein entry updated
Automatic update: comparative model was added.

Feb. 23, 2019: Protein entry updated
Automatic update: model status changed

Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 172860 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).