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      PEDF and its roles in physiological and pathological conditions: implication in diabetic and hypoxia-induced angiogenic diseases

      review-article
      Author(s): * , * , * , * ,
      Publication date (Electronic):
      Journal: Clinical Science (London, England : 1979)
      Publisher: Portland Press Ltd.
      Keywords: angiogenesis, diabetes, hypoxia, pigment epithelium-derived factor (PEDF), PEDF receptor, serpin, tissue distribution, AGE, advanced glycation end-product, ATGL, adipose triglyceride lipase, ATRA, all-trans retinoic acid, bFGF, basic fibroblast growth factor, c-FLIP, cellular FLICE-like inhibitory protein, CK2, casein kinase 2, DR, diabetic retinopathy, E, embryonic day, ERK, extracellular-signal-regulated kinase, ER, oestrogen receptor, FasL, Fas ligand, Flt-1, FMS-like tyrosine kinase 1, HIF-1, hypoxia-inducible factor 1, HUVEC, human umbilical vein endothelial cell, IκB, inhibitor of κB kinase, IGF, insulin-like growth factor, JNK, c-Jun N-terminal kinases, KDR, kinase insert domain receptor, LR, laminin receptor, LRP, low-density lipoprotein receptor-related protein, MAPK, mitogen-activated protein kinase, MEK5, MAPK/ERK kinase 5, MMP, matrix metalloproteinase, NFAT, nuclear factor of activated T-cells, NFATc2, nuclear factor of activated T-cells cytoplasmic 2, NF-κB, nuclear factor κB, OIR, oxygen-induced retinopathy, PAI-1, plaminogen activator inhibitor-1, PEDF, pigment epithelium-derived factor, PEDF-R, PEDF receptor, PEDF-tg, transgenic overexpression of PEDF, PDGF, platelet-derived growth factor, PKA, protein kinase A, PPAR-γ, peroxisome proliferator-activated receptor γ, RAR, retinoic acid receptor, RARE, retinoic acid-response element, RCL, reactive centre loop, RPE, retinal pigment epithelial, RXR, retinoid X receptor, serpin, serine proteinase inhibitor, VEGF, vascular endothelial growth factor

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          Abstract

          Pigment epithelium-derived factor (PEDF) is a broadly expressed multifunctional member of the serine proteinase inhibitor (serpin) family. This widely studied protein plays critical roles in many physiological and pathophysiological processes, including neuroprotection, angiogenesis, fibrogenesis and inflammation. The present review summarizes the temporal and spatial distribution patterns of PEDF in a variety of developing and adult organs, and discusses its functions in maintaining physiological homoeostasis. The major focus of the present review is to discuss the implication of PEDF in diabetic and hypoxia-induced angiogenesis, and the pathways mediating PEDF's effects under these conditions. Furthermore, the regulatory mechanisms of PEDF expression, function and degradation are also reviewed. Finally, the therapeutic potential of PEDF as an anti-angiogenic drug is briefly summarized.

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          WNT signaling in bone homeostasis and disease: from human mutations to treatments.

          Roland Baron, Michaela Kneissel (2013)
          Low bone mass and strength lead to fragility fractures, for example, in elderly individuals affected by osteoporosis or children with osteogenesis imperfecta. A decade ago, rare human mutations affecting bone negatively (osteoporosis-pseudoglioma syndrome) or positively (high-bone mass phenotype, sclerosteosis and Van Buchem disease) have been identified and found to all reside in components of the canonical WNT signaling machinery. Mouse genetics confirmed the importance of canonical Wnt signaling in the regulation of bone homeostasis, with activation of the pathway leading to increased, and inhibition leading to decreased, bone mass and strength. The importance of WNT signaling for bone has also been highlighted since then in the general population in numerous genome-wide association studies. The pathway is now the target for therapeutic intervention to restore bone strength in millions of patients at risk for fracture. This paper reviews our current understanding of the mechanisms by which WNT signalng regulates bone homeostasis.
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            The future of peptide-based drugs.

            David J. Craik, David Fairlie, Spiros Liras … (2013)
            The suite of currently used drugs can be divided into two categories - traditional 'small molecule' drugs with typical molecular weights of 5000 Da that are not orally bioavailable and need to be delivered via injection. Due to their small size, conventional small molecule drugs may suffer from reduced target selectivity that often ultimately manifests in human side-effects, whereas protein therapeutics tend to be exquisitely specific for their targets due to many more interactions with them, but this comes at a cost of low bioavailability, poor membrane permeability, and metabolic instability. The time has now come to reinvestigate new drug leads that fit between these two molecular weight extremes, with the goal of combining advantages of small molecules (cost, conformational restriction, membrane permeability, metabolic stability, oral bioavailability) with those of proteins (natural components, target specificity, high potency). This article uses selected examples of peptides to highlight the importance of peptide drugs, some potential new opportunities for their exploitation, and some difficult challenges ahead in this field. © 2012 John Wiley & Sons A/S.
            Article 0 comments Cited 459 times – based on 0 reviews     Review now
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              Oxygen-induced retinopathy in the mouse.

              L. Smith, E Wesolowski, A. McLellan … (1994)
              To develop oxygen-induced retinopathy in the mouse with reproducible and quantifiable proliferative retinal neovascularization suitable for examining pathogenesis and therapeutic intervention for retinal neovascularization in retinopathy of prematurity (ROP) and other vasculopathologies. One-week-old C57BL/6J mice were exposed to 75% oxygen for 5 days and then to room air. A novel fluorescein-dextran perfusion method has been developed to assess the vascular pattern. The proliferative neovascular response was quantified by counting the nuclei of new vessels extending from the retina into the vitreous in 6 microns sagittal cross-sections. Cross-sections were also stained for glial fibrillary acidic protein (GFAP). Fluorescein-dextran angiography delineated the entire vascular pattern, including neovascular tufts in flat-mounted retinas. Hyperoxia-induced neovascularization occurred at the junction between the vascularized and avascular retina in the mid-periphery. Retinal neovascularization occurred in all the pups between postnatal day 17 and postnatal day 21. There was a mean of 89 neovascular nuclei per cross-section of 9 eyes in hyperoxia compared to less than 1 nucleus per cross-section of 8 eyes in the normoxia control (P < 0.0001). Proliferative vessels were not associated with GFAP-positive astrocyte processes. The authors have described a reproducible and quantifiable mouse model of oxygen-induced retinal neovascularization that should prove useful for the study of pathogenesis of retinal neovascularization as well as for the study of medical intervention for ROP and other retinal angiopathies.
              Article 0 comments Cited 339 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Clin Sci (Lond)
                Journal ID (iso-abbrev): Clin. Sci
                Journal ID (pmc): cls
                Journal ID (publisher-id): CS
                Title: Clinical Science (London, England : 1979)
                Publisher: Portland Press Ltd.
                ISSN (Print): 0143-5221
                ISSN (Electronic): 1470-8736
                Publication date (Electronic): 19 March 2015
                Publication date (Print): 1 June 2015
                Volume: 128
                Issue: Pt 11
                Pages: 805-823
                Affiliations
                *Department of Physiology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
                Author notes
                Correspondence: Dr Jian-xing Ma (email jian-xing-ma@ 123456ouhsc.edu ).
                Article
                Publisher ID: CS20130463
                DOI: 10.1042/CS20130463
                PMC ID: 4557399
                PubMed ID: 25881671
                SO-VID: c8610a5a-0dc4-40ec-92f6-421c5fb11fd9
                Copyright © © 2015 The author(s) has paid for this article to be freely available under the terms of the Creative Commons Attribution Licence (CC-BY)(http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 2 August 2013
                Date revision received : 1 December 2014
                Date accepted : 22 December 2014
                Page count
                Figures: 2, Tables: 1, References: 258, Pages: 19
                Categories
                Subject: Review Article
                Subject: S9

                ScienceOpen disciplines: Medicine
                Keywords: angiogenesis,diabetes,hypoxia,pigment epithelium-derived factor (pedf),pedf receptor,serpin,tissue distribution,age, advanced glycation end-product,atgl, adipose triglyceride lipase,atra, all-trans retinoic acid,bfgf, basic fibroblast growth factor,c-flip, cellular flice-like inhibitory protein,ck2, casein kinase 2,dr, diabetic retinopathy, e, embryonic day,erk, extracellular-signal-regulated kinase,er, oestrogen receptor,fasl, fas ligand,flt-1, fms-like tyrosine kinase 1,hif-1, hypoxia-inducible factor 1,huvec, human umbilical vein endothelial cell,iκb, inhibitor of κb kinase,igf, insulin-like growth factor,jnk, c-jun n-terminal kinases,kdr, kinase insert domain receptor,lr, laminin receptor,lrp, low-density lipoprotein receptor-related protein,mapk, mitogen-activated protein kinase,mek5, mapk/erk kinase 5,mmp, matrix metalloproteinase,nfat, nuclear factor of activated t-cells,nfatc2, nuclear factor of activated t-cells cytoplasmic 2,nf-κb, nuclear factor κb,oir, oxygen-induced retinopathy,pai-1, plaminogen activator inhibitor-1,pedf, pigment epithelium-derived factor,pedf-r, pedf receptor,pedf-tg, transgenic overexpression of pedf,pdgf, platelet-derived growth factor,pka, protein kinase a,ppar-γ, peroxisome proliferator-activated receptor γ,rar, retinoic acid receptor,rare, retinoic acid-response element,rcl, reactive centre loop,rpe, retinal pigment epithelial,rxr, retinoid x receptor,serpin, serine proteinase inhibitor,vegf, vascular endothelial growth factor
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: angiogenesis, diabetes, hypoxia, pigment epithelium-derived factor (pedf), pedf receptor, serpin, tissue distribution, age, advanced glycation end-product, atgl, adipose triglyceride lipase, atra, all-trans retinoic acid, bfgf, basic fibroblast growth factor, c-flip, cellular flice-like inhibitory protein, ck2, casein kinase 2, dr, diabetic retinopathy, e, embryonic day, erk, extracellular-signal-regulated kinase, er, oestrogen receptor, fasl, fas ligand, flt-1, fms-like tyrosine kinase 1, hif-1, hypoxia-inducible factor 1, huvec, human umbilical vein endothelial cell, iκb, inhibitor of κb kinase, igf, insulin-like growth factor, jnk, c-jun n-terminal kinases, kdr, kinase insert domain receptor, lr, laminin receptor, lrp, low-density lipoprotein receptor-related protein, mapk, mitogen-activated protein kinase, mek5, mapk/erk kinase 5, mmp, matrix metalloproteinase, nfat, nuclear factor of activated t-cells, nfatc2, nuclear factor of activated t-cells cytoplasmic 2, nf-κb, nuclear factor κb, oir, oxygen-induced retinopathy, pai-1, plaminogen activator inhibitor-1, pedf, pigment epithelium-derived factor, pedf-r, pedf receptor, pedf-tg, transgenic overexpression of pedf, pdgf, platelet-derived growth factor, pka, protein kinase a, ppar-γ, peroxisome proliferator-activated receptor γ, rar, retinoic acid receptor, rare, retinoic acid-response element, rcl, reactive centre loop, rpe, retinal pigment epithelial, rxr, retinoid x receptor, serpin, serine proteinase inhibitor, vegf, vascular endothelial growth factor

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