PEDF, PPAR-γ, p53: Deadly circuits arise when worlds collide

Abstract

See article by Ho et al. [6] (pages 213–223) in this issue. The superfamily of serine proteinase inhibitors (serpins) is involved in a number of fundamental biological processes such as blood coagulation, complement activation, fibrinolysis, angiogenesis, inflammation and tumor suppression and are expressed in a cell-specific manner [1]. The pigment epithelium-derived factor (PEDF) is a 50-kD serpin that lacks inhibitory properties against either serine or cysteine proteinases [2]. PEDF was first identified in 1987 by Tombran-Tink and Johnson in conditioned medium from foetal human retinal pigment epithelium cell cultures (published in 1991 [3]). PEDF has been shown to be a neurotrophic/differentiation factor and an inhibitor of glial cell proliferation [4]. It is also a protein that is highly up-regulated in the G0 phase of early-passage cells compared with rapidly proliferating cells or senescent cells, and is thus also linked to both the cell cycle and cell senescence. Low-dose PEDF inhibits endothelial cell migration and proliferation, reducing VEGF, FGF-2 and other cytokines-dependent angiogenesis in the rat cornea, and, recently, PEDF has been found to be involved in endothelial cell apoptosis via FAS ligand (FASL) induction and caspase 8 and 9 activation. Although many findings suggest a receptor-like nature of PEDF action, the … *Corresponding author. Tel.: +39 0666462431; fax: +39 0666462430. gaetano{at}idi.it