PEDF: A pigment epithelium-derived factor with potent neuronal differentiative activity

Tombran-Tink, Joyce; Chader, G.; Johnson, Lincoln V.

doi:10.1016/0014-4835(91)90248-d

Cited by 542 publications

(376 citation statements)

References 11 publications

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“…Biochemical and immunochemical studies have identified PEDF as a soluble extracellular protein localized in washes of the interphotoreceptor matrix (IPM), vitreous and aqueous of several mammalian species (Tombran-Tink et al, 1995;Wu et al, 1995;Ortego et al, 1996;Alberdi et al, 1998;Karakousis et al, 2001). PEDF, discovered as a product secreted by cultured RPE cells from fetal human eyes (Tombran Tink, 1991), can be released from a variety of cells, including stably transfected eukaryotic cells with full length PEDF cDNA under the control of recombinant transcriptional promoters (Stratikos et al, 1996;Perez-Mediavilla et al, 1998). By sequence homology, PEDF is a member of the serpin superfamily , formed by proteins with a common overall protein conformation with a variety of biological functions, most of which are extracellular serine protease inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Pigment epithelium-derived factor in the monkey retinal pigment epithelium and interphotoreceptor matrix: apical secretion and distribution

Becerra

Fariss

et al. 2004

Experimental Eye Research

111

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Pigment epithelium-derived factor (PEDF) is an extracellular protein derived from the retinal pigment epithelium (RPE), a tissue formed by polarized cells that release growth and trophic factors in a directional fashion. We have investigated the distribution and directional release of PEDF protein by the monkey RPE. We established primary cultures of monkey RPE cells that expressed the PEDF gene, and that synthesized and secreted the PEDF protein. Northern analysis of RPE cultures and monkey ocular tissues showed that PEDF transcripts were highly expressed in RPE as compared with several other monkey ocular tissues, being even more abundant in cultured cells than they were in the native RPE. The differentiated RPE cells in culture secreted protein that shared the immunological, biochemical and biological characteristics of PEDF. The overall PEDF levels in the RPE conditioned media reached 6·5 mg ml 2 after 8 days in culture (i.e. 1·1 pg of PEDF per RPE cell). RPE cells were cultivated on permeable supports as monolayers forming a barrier between apical and basal compartments. Apical and basal culture media were sampled at three or four-day intervals for 18 cycles, and the PEDF content was quantified. Most of the PEDF protein was significantly higher in the apical than in the basal medium (. 4 times) at the initial recovery intervals, to be detected only in the apical medium at the latter intervals. In the native monkey eye, the concentration of soluble PEDF in the interphotoreceptor matrix (144 nM) was 7-fold and 25-fold greater than in vitreous and aqueous, respectively. PEDF was abundant in the interphotoreceptor matrix surrounding rod and cone outer segments, and was detectable at lower levels in the RPE as visualized by confocal microscopy. We concluded that PEDF synthesized by the RPE is secreted preferentially from the apical surface and is distributed apically to the RPE bordering the outer segments of photoreceptors. PEDF can be a useful marker for RPE polarization and differentiation. The polarization of RPE may be an important mechanism to control PEDF secretion and our results offer interesting possibilities on regulation of PEDF. q

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Section: Introductionmentioning

confidence: 99%

Pigment epithelium-derived factor in the monkey retinal pigment epithelium and interphotoreceptor matrix: apical secretion and distribution

Becerra

Fariss

et al. 2004

Experimental Eye Research

111

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“…9 It was first purified from the conditioned media of human retinal pigment epithelial cells as a factor with potent neuronal differentiating activity. 9 Recently, PEDF has been shown to be produced from a variety of tissues, including vascular cells, inflammatory cells, and adipocytes. 10 -13 Furthermore, we and others have found that PEDF blocks cytokine-or growth factor-induced endothelial cell damage, platelet aggregation, and T-cell activation in vitro through its anti-oxidative and anti-inflammatory properties.…”

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Administration of Pigment Epithelium-Derived Factor Inhibits Left Ventricular Remodeling and Improves Cardiac Function in Rats with Acute Myocardial Infarction

Ueda

Yamagishi

Matsui

et al. 2011

The American Journal of Pathology

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Oxidative stress and inflammation are involved in cardiac remodeling after acute myocardial infarction (AMI). We have found that pigment epithelium-derived factor (PEDF) inhibits vascular inflammation through its anti-oxidative properties. However, effects of PEDF on cardiac remodeling after AMI remain unknown. We investigated whether PEDF could inhibit left ventricular remodeling and improve cardiac function in rats with AMI. AMI was induced in 8-weekold Sprague-Dawley rats by ligation of the left ascending coronary artery. Rats were treated intravenously with vehicle or 10 g PEDF/100 g b.wt. every day for up to 2 weeks after AMI. Each rat was followed until 16 weeks of age. PEDF levels in infarcted areas and serum were significantly decreased at 1 week after AMI and remained low during the observational periods. PEDF administration inhibited apoptotic cell death and oxidative stress generation around the infarcted areas at 2 and 8 weeks after AMI. Further, PEDF injection suppressed cardiac fibrosis by reducing transforming growth factor-␤ and type III collagen expression, improved left ventricular ejection fraction, ameliorated diastolic dysfunction, and inhibited the increase in left ventricular mass index at 8 weeks after AMI. The present study demonstrated that PEDF could inhibit tissue remodeling and improve cardiac function in AMI rats. Substitution of PEDF may be a novel therapeutic strategy for cardiac remodeling after AMI.

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“…1,2 It shares high sequence homology with other serine proteinase inhibitors (serpins) and behaves like a noninhibitory serpin. 3 PEDF is found in a broad range of human fetal and adult tissues, including almost all brain areas.…”

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Inhibition of glioma invasion by overexpression of pigment epithelium-derived factor

et al. 2004

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Pigment epithelium-derived factor (PEDF) is a potent inhibitor of angiogenesis and an inducer of neural differentiation. We previously reported the loss of PEDF expression in glioma progression. In this study, we investigated whether PEDF overexpression could suppress glioma growth and invasion. Glioma cell line U251 was stably transfected with a full-length human PEDF expression vector. The expression and release of various cytokines and angiogenic factors into the medium were analyzed by realtime reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, and gelatin zymography. Apoptosis was checked by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. Growth inhibition was evaluated by using the in vitro Matrigel invasion. Tumorigenicity was examined in vivo by subcutaneous xenotransplantation into severe combined immunodeficient mice. In U251 cells overexpressing PEDF, thrombospondin-1 protein was upregulated (5.3-fold more), but the production of vascular endothelial growth factor (VEGF) (1.8-fold less) and basic fibroblast growth factor (2.5-fold less) was lower than in cells transfected with the vector only. PEDF also downregulated the production of matrix metalloproteinase-9. Conditioned medium collected from the PEDF-transfected U251 cells showed a significant reduction of VEGF expression. In vitro invasiveness was reduced by approximately 40%. PEDF expression prevented the growth of transfected cells and caused a significant increase in the percentage of cells undergoing apoptosis (50.4% in PEDF-transfected cells). Furthermore, the size of xenotransplants was significantly smaller. In conclusion, PEDF overexpression decreased malignancy, and this might be attributed to the promotion of apoptosis and the regulation of expression of angiogenic effectors. Thus, treatment with PEDF may be useful in patients with malignant gliomas. However, the mechanism of apoptosis induction needs to be investigated.

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PEDF: A pigment epithelium-derived factor with potent neuronal differentiative activity

Cited by 542 publications

References 11 publications

Pigment epithelium-derived factor in the monkey retinal pigment epithelium and interphotoreceptor matrix: apical secretion and distribution

Pigment epithelium-derived factor in the monkey retinal pigment epithelium and interphotoreceptor matrix: apical secretion and distribution

Administration of Pigment Epithelium-Derived Factor Inhibits Left Ventricular Remodeling and Improves Cardiac Function in Rats with Acute Myocardial Infarction

Inhibition of glioma invasion by overexpression of pigment epithelium-derived factor

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