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Pigment Epithelium-Derived Factor (PEDF): A Multifaceted and Functional New Therapeutic Agent

Yıl 2015, Cilt: 24 Sayı: 3, 283 - 295, 14.09.2015
https://doi.org/10.17827/aktd.14318

Öz

Pigment epithelium-derived factor, a noninhibitory member of the serine protease inhibitor (serpin) family, is a naturally-occurring protein. The gene encoding human pigment epithelium-derived factor was localized to 17th chromosome and is around 16 kb. Mature gene product is 50 kDa and secreted as a soluable monomeric glycoprotein. Current studies show that pigment epithelium-derived factor is not only found in retinal pigment epithelium cells, but also widely expressed throughout the human body and in the tissues of almost all mammals. Pigment epithelium-derived factor was first discovered as a neurotrophic factor, an inducer of retinoblastoma cell differentiation, secreted by retinal pigment epithelial cells. Later, multiple and varied biological activities of pigment epithelium-derived factor have been found. The unique medicinal properties of this interesting protein are; anti-angiogenesis, anti-proliferative, tumor cell differentiation, anti-oxidant, and neuroprotective effects. Due to all these effects, recently pigment epithelium-derived factor has become the focus of attention of research topics. Today, studies focus on pigment epithelium-derived factor’s indirect (anti-angiogenesis) and direct antitumor effects (inhibiting cell division, tumor invasion and metastasis, promoting tumor cell apoptosis and differentiation). Thus, it is an emerging anti-tumor agent that may be able to target tumor cells and may be used instead of conventional chemotherapy in the future. In this review; briefly the structure and functions of pigment epithelium-derived factor, and the mechanisms in which pigment epithelium-derived factor plays an active role will be discussed.

Kaynakça

  • Steele FR, Chader GJ, Johnson LV, Tombran-Tink J. Pigment epithelium-derived factor: neurotrophic activity and identification as a member of the serine protease inhibitor gene family. Proc Natl Acad Sci. 1993;90:1526–30.
  • Fernandez-Garcia NI, Volpert OV, Jimenez B. Pigment epithelium-derived factor as a multifunctional antitumor factor. J Mol Med Berl. 2007;85:15–22.
  • Tombran-Tink J, Shivaram SM, Chader GJ, Johnson LV, Bok D. Expression, secretion, and age- related downregulation of pigment epithelium-derived factor, a serpin with neurotrophic activity. J Neurosci. 1995;15:4992–5003.
  • Becerra SP. Focus on Molecules: Pigment epithelium-derived factor (PEDF). Exp Eye Res. 2006;82:739–40.
  • Becerra SP, Sagasti A, Spinella P, Notario V. Pigment epithelium-derived factor behaves like a noninhibitory serpin. Neurotrophic activity does not require the serpin reactive loop. J Biol Chem. 1995;270:25992–9.
  • Tombran-Tink J, Mazuruk K, Rodriguez IR, Chung D, Linker T, Englander E et al. Organization, evolutionary conservation, expression and unusual Alu density of the human gene for pigment epithelium-derived factor, a unique neurotrophic serpin. Mol Vis. 1996;2:11.
  • Tombran-Tink J, Pawar H, Swaroop A, Rodriguez I, Chader GJ. Localization of the gene for pigment epithelium-derived factor (PEDF) to chromosome 17p13.1 and expression in cultured human retinoblastoma cells. Genomics. 1994;19:266–72.
  • Craword SE, Fitchev P, Veliceasa D, Volpert OV. The many facets of PEDF in drug discovery and disease: a diamond in the rough or split personality disorder? Expert Opin Drug Discov. 2013;8:769–92.
  • Yasui N, Mori T, Morito D, Matsushita O, Kourai H, Nagata K et al. Dual-site recognition of different extracellular matrix components by anti-angiogenic/neurotrophic serpin, PEDF. Biochemistry (Mosc.). 2003;42:3160–7.
  • Hosomichi J, Yasui N, Koide T, Soma K, Morita I. Involvement of the collagen I-binding motif in the anti-angiogenic activity of pigment epithelium-derived factor. Biochem Biophys Res Commun. 2005;335:756–61.
  • Filleur S, Volz K, Nelius T, Mirochnik Y, Huang H, Zaichuk T et al. Two Functional Epitopes of Pigment Epithelial–Derived Factor Block Angiogenesis and Induce Differentiation in Prostate Cancer. Cancer Res. 2005;65:5144–52.
  • Alberdi E, Aymerich MS, Becerra SP. Binding of pigment epithelium-derived factor (PEDF) to retinoblastoma cells and cerebellar granule neurons. Evidence for a PEDF receptor. J Biol Chem. 1999;274:31605–12.
  • Aymerich MS, Alberdi EM, Martínez A, Becerra SP. Evidence for pigment epithelium-derived factor receptors in the neural retina. Invest Ophthalmol Vis Sci. 2001;42:3287–93.
  • Bilak MM, Becerra SP, Vincent AM, Moss BH, Aymerich MS, Kuncl RW. Identification of the neuroprotective molecular region of pigment epithelium-derived factor and its binding sites on motor neurons. J Neurosci. 2002;22:9378–86.
  • Mirochnik Y, Aurora A, Schulze-Hoepfner F, Deabes A, Shifrin V, Beckmann R et al. Short Pigment Epithelial-Derived Factor-Derived Peptide Inhibits Angiogenesis and Tumor Growth. Clin Cancer Res. 2009;15:1655–63.
  • Dawson DW, Volpert OV, Gillis P, Crawford SE, Xu H, Benedict W et al. Pigment epithelium- derived factor: a potent inhibitor of angiogenesis. Science. 1999;285:245–8.
  • Bouck N. PEDF: anti-angiogenic guardian of ocular function. Trends Mol Med. 2002;8:330–4.
  • Renno RZ, Youssri AI, Michaud N, Gragoudas ES, Miller JW. Expression of pigment epithelium- derived factor in experimental choroidal neovascularization. Invest Ophthalmol Vis Sci.
  • Spranger J, Osterhoff M, Reimann M, Möhlig M, Ristow M, Francis MK et al. Loss of the antiangiogenic pigment epithelium-derived factor in patients with angiogenic eye disease. Diabetes. 2001;50:2641–5.
  • Volpert OV, Zaichuk T, Zhou W, Reiher F, Ferguson T, Stuart PM et al. Inducer-stimulated Fas targets activated endothelium for destruction by anti-angiogenic thrombospondin-1 and pigment epithelium-derived factor. Nat Med. 2002;8:349–57.
  • Halin S, Wikström P, Rudolfsson S, Stattin P, Doll JA, Crawford SE et al. Decreased pigment epithelium-derived factor is associated with metastatic phenotype in human and rat prostate tumors. Cancer Res. 2004;64:5664–71.
  • Uehara H, Miyamoto M, Kato K, Ebihara Y, Kaneko H, Hashimoto H et al. Expression of pigment epithelium-derived factor decreases liver metastasis and correlates with favorable prognosis for patients with ductal pancreatic adenocarcinoma. Cancer Res. 2004;64:3533–7.
  • Crawford SE, Stellmach V, Ranalli M, Huang X, Volpert O, De Vries GH et al. Pigment epithelium- derived factor (PEDF) in neuroblastoma: a multifunctional mediator of Schwann cell antitumor activity. J Cell Sci. 2001;114:4421–8.
  • Guan M, Yam HF, Su B, Chan KP, Pang CP, Liu WW et al. Loss of pigment epithelium derived factor expression in glioma progression. J Clin Pathol. 2003;56:277–82.
  • Hase R, Miyamoto M, Uehara H, Kadoya M, Ebihara Y, Murakami Y et al. Pigment epithelium- derived factor gene therapy inhibits human pancreatic cancer in mice. Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res. 2005;11:8737–44.
  • Garcia M, Fernandez-Garcia N, Rivas V, Carretero M, Escamez MJ, Gonzalez-Martin A et al. Inhibition of xenografted human melanoma growth and prevention of metastasis development by dual antiangiogenic/antitumor activities of pigment epithelium-derived factor. Cancer Res. 2004;64:5632–42.
  • Abe R, Shimizu T, Yamagishi S, Shibaki A, Amano S, Inagaki Y et al. Overexpression of pigment epithelium-derived factor decreases angiogenesis and inhibits the growth of human malignant melanoma cells in vivo. Am J Pathol. 2004;164:1225–32.
  • Takenaka K, Yamagishi SI, Jinnouchi Y, Nakamura K, Matsui T, Imaizumi T. Pigment epithelium- derived factor (PEDF)-induced apoptosis and inhibition of vascular endothelial growth factor (VEGF) expression in MG63 human osteosarcoma cells. Life Sci. 2005;77:3231–41.
  • Fitzgerald DP, Subramanian P, Deshpande M, Graves C, Gordon I, Qian Y et al. Opposing effects of pigment epithelium-derived factor on breast cancer cell versus neuronal survival: implication for brain metastasis and metastasis-induced brain damage. Cancer Res. 2012;72:144–53.
  • Ogata N, Wang L, Jo N, Tombran-Tink J, Takahashi K, Mrazek D et al. Pigment epithelium derived factor as a neuroprotective agent against ischemic retinal injury. Curr Eye Res. 2001;22:245–52.
  • Stellmach V, Crawford SE, Zhou W, Bouck N. Prevention of ischemia-induced retinopathy by the natural ocular antiangiogenic agent pigment epithelium-derived factor. Proc Natl Acad Sci. 2001;98:2593–7.
  • Takita H, Yoneya S, Gehlbach PL, Duh EJ, Wei LL, Mori K. Retinal neuroprotection against ischemic injury mediated by intraocular gene transfer of pigment epithelium-derived factor. Invest Ophthalmol Vis Sci. 2003;44:4497–4504.
  • Li H, Tran VV, Hu Y, Mark Saltzman W, Barnstable CJ, Tombran-Tink J. A PEDF N-terminal peptide protects the retina from ischemic injury when delivered in PLGA nanospheres. Exp Eye Res. 2006;83:824–33.
  • Unterlauft JD, Eichler W, Kuhne K, Yang XM, Yafai Y, Wiedemann P et al. Pigment epithelium- derived factor released by Müller glial cells exerts neuroprotective effects on retinal ganglion cells. Neurochem Res. 2012;37:1524–33.
  • Barnstable CJ, Tombran-Tink J. Neuroprotective and antiangiogenic actions of PEDF in the eye: molecular targets and therapeutic potential. Prog Retin Eye Res. 2004;23:561–77.
  • Houenou LJ, D'Costa AP, Li L, Turgeon VL, Enyadike C, Alberdi E, Becerra SP. Pigment epithelium- derived factor promotes the survival and differentiation of developing spinal motor neurons. J Comp Neurol. 1999;412:506–14.
  • Cao W, Tombran-Tink J, Chen W, Mrazek D, Elias R, McGinnis JF. Pigment epithelium-derived factor protects cultured retinal neurons against hydrogen peroxide-induced cell death. J Neurosci Res. 1999;57:789–800.
  • International Diabetes Federation. IDF Diabetes Atlas Sixth edition. http://www.idf.org/diabetesatlas (2014).
  • World Health Organisation. Prevention of Blindness from Diabetes Mellitus. http://www.who.int/blindness/Prevention%20of%20Blindness%20from%20Diabetes%20Mellit us-with-cover-small.pdf (accessed Nov 2005)
  • Ahmed, N. Advanced glycation endproducts--role in pathology of diabetic complications. Diabetes Res Clin Pract. 2005;67:3–21.
  • Yamagishi S, Hsu CC, Taniguchi M, Harada S, Yamamoto Y, Ohsawa K et al. Receptor-mediated toxicity to pericytes of advanced glycosylation end products: a possible mechanism of pericyte loss in diabetic microangiopathy. Biochem Biophys Res Commun. 1995;213:681–7.
  • Rojas A, Romay S, González D, Herrera B, Delgado R, Otero K. Regulation of endothelial nitric oxide synthase expression by albumin-derived advanced glycosylation end products. Circ Res. 2000;86:E50–4.
  • Sheikpranbabu S, Haribalaganesh R, Gurunathan S. Pigment epithelium-derived factor inhibits advanced glycation end-products-induced cytotoxicity in retinal pericytes. Diabetes Metab.
  • Yamagishi S, Inagaki Y, Amano S, Okamoto T, Takeuchi M, Makita Z. Pigment epithelium-derived factor protects cultured retinal pericytes from advanced glycation end product-induced injury through its antioxidative properties. Biochem Biophys Res Commun. 2002;296:877–82.
  • Amano S, Yamagishi S, Inagaki Y, Nakamura K, Takeuchi M, Inoue H et al. Pigment epithelium- derived factor inhibits oxidative stress-induced apoptosis and dysfunction of cultured retinal pericytes. Microvasc Res. 2005;69:45–55.
  • Yamagishi SI, Nakamura K, Ueda S, Kato S, Imaizumi T. Pigment epithelium-derived factor (PEDF) blocks angiotensin II signaling in endothelial cells via suppression of NADPH oxidase: a novel anti-oxidative mechanism of PEDF. Cell Tissue Res. 2005;320:437–45.
  • Yamagishi SI, Matsui T, Nakamura K, Yoshida T, Takeuchi M, Inoue H et al. Pigment-epithelium- derived factor suppresses expression of receptor for advanced glycation end products in the eye of diabetic rats. Ophthalmic Res. 2007;39:92–7.
  • Yamagishi S, Matsui T. Advanced glycation end products (AGEs), oxidative stress and diabetic retinopathy. Curr Pharm Biotechnol. 2011;12:362–8
  • Correspondence Address / Yazışma Adresi

Pigment Epitel Kaynaklı Faktör (PEDF): Çok Yönlü ve Fonksiyonlu Yeni Bir Terapötik Ajan

Yıl 2015, Cilt: 24 Sayı: 3, 283 - 295, 14.09.2015
https://doi.org/10.17827/aktd.14318

Öz

Pigment epitel kaynaklı faktör, non-inhibitör serin proteaz inhibitör (serpin) ailesinin bir üyesi olup doğal oluşan bir proteindir. İnsan pigment epitel kaynaklı faktör geni 17. kromozom üzerinde lokalize olmuş ~yaklaşık 16 kb uzunluğunda bir gendir. Olgun gen ürünü çoğunlukla 50 kDa ağırlığında çözünür monomerik bir glikoprotein olarak salınmaktadır. Mevcut çalışmalar pigment epitel kaynaklı faktörünün sadece gözdeki retinal pigment epitel hücrelerinde değil, insan vücudunda ve hemen hemen tüm memeli dokularında da ifade olduğunu göstermektedir. Pigment epitel kaynaklı faktör ilk defa retinal pigment epitelyal hücrelerinden salınan, retinoblastoma hücrelerinin farklılaşmasını indükleyen nörotrofik bir faktör olarak keşfedilmiştir. Fakat sonraları pigment epitel kaynaklı faktörünün çok sayıda ve çeşitli biyolojik aktivitelere sahip olduğu ortaya çıkmıştır. Bu ilginç proteinin antianjiyogenez, antiproliferatif, tümör hücre farklılaşması, anti-oksidan ve nöroprotektif etkileri gibi eşsiz tıbbi özellikleri vardır. Tüm bu etkiler, son zamanlarda pigment epitel kaynaklı faktörünü araştırma konularının ilgi odağı haline getirmiştir. Bugünlerde çalışmalar pigment epitel kaynaklı faktörünün dolaylı (anti-anjiyogenez) ve direk anti-tümör etkileri (hücre bölünmesinin, tümör invazyonunun ve metastazın inhibisyonu, tümör hücre apoptoz ve farklılaşmasını teşviki gibi) üzerine yoğunlaşmıştır. Bu nedenle pigment epitel kaynaklı faktör, tümör hücrelerini hedef alabilen ve gelecekte geleneksel kemoterapinin yerine kullanılabilecek umut vaat eden bir anti-tümör ajanı olarak görülmektedir. Bu derlemede; Pigment epitel kaynaklı faktörünün yapısı ve fonksiyonlarından kısaca bahsedilerek, etkin rol oynadığı mekanizmalara değinilecektir.

Kaynakça

  • Steele FR, Chader GJ, Johnson LV, Tombran-Tink J. Pigment epithelium-derived factor: neurotrophic activity and identification as a member of the serine protease inhibitor gene family. Proc Natl Acad Sci. 1993;90:1526–30.
  • Fernandez-Garcia NI, Volpert OV, Jimenez B. Pigment epithelium-derived factor as a multifunctional antitumor factor. J Mol Med Berl. 2007;85:15–22.
  • Tombran-Tink J, Shivaram SM, Chader GJ, Johnson LV, Bok D. Expression, secretion, and age- related downregulation of pigment epithelium-derived factor, a serpin with neurotrophic activity. J Neurosci. 1995;15:4992–5003.
  • Becerra SP. Focus on Molecules: Pigment epithelium-derived factor (PEDF). Exp Eye Res. 2006;82:739–40.
  • Becerra SP, Sagasti A, Spinella P, Notario V. Pigment epithelium-derived factor behaves like a noninhibitory serpin. Neurotrophic activity does not require the serpin reactive loop. J Biol Chem. 1995;270:25992–9.
  • Tombran-Tink J, Mazuruk K, Rodriguez IR, Chung D, Linker T, Englander E et al. Organization, evolutionary conservation, expression and unusual Alu density of the human gene for pigment epithelium-derived factor, a unique neurotrophic serpin. Mol Vis. 1996;2:11.
  • Tombran-Tink J, Pawar H, Swaroop A, Rodriguez I, Chader GJ. Localization of the gene for pigment epithelium-derived factor (PEDF) to chromosome 17p13.1 and expression in cultured human retinoblastoma cells. Genomics. 1994;19:266–72.
  • Craword SE, Fitchev P, Veliceasa D, Volpert OV. The many facets of PEDF in drug discovery and disease: a diamond in the rough or split personality disorder? Expert Opin Drug Discov. 2013;8:769–92.
  • Yasui N, Mori T, Morito D, Matsushita O, Kourai H, Nagata K et al. Dual-site recognition of different extracellular matrix components by anti-angiogenic/neurotrophic serpin, PEDF. Biochemistry (Mosc.). 2003;42:3160–7.
  • Hosomichi J, Yasui N, Koide T, Soma K, Morita I. Involvement of the collagen I-binding motif in the anti-angiogenic activity of pigment epithelium-derived factor. Biochem Biophys Res Commun. 2005;335:756–61.
  • Filleur S, Volz K, Nelius T, Mirochnik Y, Huang H, Zaichuk T et al. Two Functional Epitopes of Pigment Epithelial–Derived Factor Block Angiogenesis and Induce Differentiation in Prostate Cancer. Cancer Res. 2005;65:5144–52.
  • Alberdi E, Aymerich MS, Becerra SP. Binding of pigment epithelium-derived factor (PEDF) to retinoblastoma cells and cerebellar granule neurons. Evidence for a PEDF receptor. J Biol Chem. 1999;274:31605–12.
  • Aymerich MS, Alberdi EM, Martínez A, Becerra SP. Evidence for pigment epithelium-derived factor receptors in the neural retina. Invest Ophthalmol Vis Sci. 2001;42:3287–93.
  • Bilak MM, Becerra SP, Vincent AM, Moss BH, Aymerich MS, Kuncl RW. Identification of the neuroprotective molecular region of pigment epithelium-derived factor and its binding sites on motor neurons. J Neurosci. 2002;22:9378–86.
  • Mirochnik Y, Aurora A, Schulze-Hoepfner F, Deabes A, Shifrin V, Beckmann R et al. Short Pigment Epithelial-Derived Factor-Derived Peptide Inhibits Angiogenesis and Tumor Growth. Clin Cancer Res. 2009;15:1655–63.
  • Dawson DW, Volpert OV, Gillis P, Crawford SE, Xu H, Benedict W et al. Pigment epithelium- derived factor: a potent inhibitor of angiogenesis. Science. 1999;285:245–8.
  • Bouck N. PEDF: anti-angiogenic guardian of ocular function. Trends Mol Med. 2002;8:330–4.
  • Renno RZ, Youssri AI, Michaud N, Gragoudas ES, Miller JW. Expression of pigment epithelium- derived factor in experimental choroidal neovascularization. Invest Ophthalmol Vis Sci.
  • Spranger J, Osterhoff M, Reimann M, Möhlig M, Ristow M, Francis MK et al. Loss of the antiangiogenic pigment epithelium-derived factor in patients with angiogenic eye disease. Diabetes. 2001;50:2641–5.
  • Volpert OV, Zaichuk T, Zhou W, Reiher F, Ferguson T, Stuart PM et al. Inducer-stimulated Fas targets activated endothelium for destruction by anti-angiogenic thrombospondin-1 and pigment epithelium-derived factor. Nat Med. 2002;8:349–57.
  • Halin S, Wikström P, Rudolfsson S, Stattin P, Doll JA, Crawford SE et al. Decreased pigment epithelium-derived factor is associated with metastatic phenotype in human and rat prostate tumors. Cancer Res. 2004;64:5664–71.
  • Uehara H, Miyamoto M, Kato K, Ebihara Y, Kaneko H, Hashimoto H et al. Expression of pigment epithelium-derived factor decreases liver metastasis and correlates with favorable prognosis for patients with ductal pancreatic adenocarcinoma. Cancer Res. 2004;64:3533–7.
  • Crawford SE, Stellmach V, Ranalli M, Huang X, Volpert O, De Vries GH et al. Pigment epithelium- derived factor (PEDF) in neuroblastoma: a multifunctional mediator of Schwann cell antitumor activity. J Cell Sci. 2001;114:4421–8.
  • Guan M, Yam HF, Su B, Chan KP, Pang CP, Liu WW et al. Loss of pigment epithelium derived factor expression in glioma progression. J Clin Pathol. 2003;56:277–82.
  • Hase R, Miyamoto M, Uehara H, Kadoya M, Ebihara Y, Murakami Y et al. Pigment epithelium- derived factor gene therapy inhibits human pancreatic cancer in mice. Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res. 2005;11:8737–44.
  • Garcia M, Fernandez-Garcia N, Rivas V, Carretero M, Escamez MJ, Gonzalez-Martin A et al. Inhibition of xenografted human melanoma growth and prevention of metastasis development by dual antiangiogenic/antitumor activities of pigment epithelium-derived factor. Cancer Res. 2004;64:5632–42.
  • Abe R, Shimizu T, Yamagishi S, Shibaki A, Amano S, Inagaki Y et al. Overexpression of pigment epithelium-derived factor decreases angiogenesis and inhibits the growth of human malignant melanoma cells in vivo. Am J Pathol. 2004;164:1225–32.
  • Takenaka K, Yamagishi SI, Jinnouchi Y, Nakamura K, Matsui T, Imaizumi T. Pigment epithelium- derived factor (PEDF)-induced apoptosis and inhibition of vascular endothelial growth factor (VEGF) expression in MG63 human osteosarcoma cells. Life Sci. 2005;77:3231–41.
  • Fitzgerald DP, Subramanian P, Deshpande M, Graves C, Gordon I, Qian Y et al. Opposing effects of pigment epithelium-derived factor on breast cancer cell versus neuronal survival: implication for brain metastasis and metastasis-induced brain damage. Cancer Res. 2012;72:144–53.
  • Ogata N, Wang L, Jo N, Tombran-Tink J, Takahashi K, Mrazek D et al. Pigment epithelium derived factor as a neuroprotective agent against ischemic retinal injury. Curr Eye Res. 2001;22:245–52.
  • Stellmach V, Crawford SE, Zhou W, Bouck N. Prevention of ischemia-induced retinopathy by the natural ocular antiangiogenic agent pigment epithelium-derived factor. Proc Natl Acad Sci. 2001;98:2593–7.
  • Takita H, Yoneya S, Gehlbach PL, Duh EJ, Wei LL, Mori K. Retinal neuroprotection against ischemic injury mediated by intraocular gene transfer of pigment epithelium-derived factor. Invest Ophthalmol Vis Sci. 2003;44:4497–4504.
  • Li H, Tran VV, Hu Y, Mark Saltzman W, Barnstable CJ, Tombran-Tink J. A PEDF N-terminal peptide protects the retina from ischemic injury when delivered in PLGA nanospheres. Exp Eye Res. 2006;83:824–33.
  • Unterlauft JD, Eichler W, Kuhne K, Yang XM, Yafai Y, Wiedemann P et al. Pigment epithelium- derived factor released by Müller glial cells exerts neuroprotective effects on retinal ganglion cells. Neurochem Res. 2012;37:1524–33.
  • Barnstable CJ, Tombran-Tink J. Neuroprotective and antiangiogenic actions of PEDF in the eye: molecular targets and therapeutic potential. Prog Retin Eye Res. 2004;23:561–77.
  • Houenou LJ, D'Costa AP, Li L, Turgeon VL, Enyadike C, Alberdi E, Becerra SP. Pigment epithelium- derived factor promotes the survival and differentiation of developing spinal motor neurons. J Comp Neurol. 1999;412:506–14.
  • Cao W, Tombran-Tink J, Chen W, Mrazek D, Elias R, McGinnis JF. Pigment epithelium-derived factor protects cultured retinal neurons against hydrogen peroxide-induced cell death. J Neurosci Res. 1999;57:789–800.
  • International Diabetes Federation. IDF Diabetes Atlas Sixth edition. http://www.idf.org/diabetesatlas (2014).
  • World Health Organisation. Prevention of Blindness from Diabetes Mellitus. http://www.who.int/blindness/Prevention%20of%20Blindness%20from%20Diabetes%20Mellit us-with-cover-small.pdf (accessed Nov 2005)
  • Ahmed, N. Advanced glycation endproducts--role in pathology of diabetic complications. Diabetes Res Clin Pract. 2005;67:3–21.
  • Yamagishi S, Hsu CC, Taniguchi M, Harada S, Yamamoto Y, Ohsawa K et al. Receptor-mediated toxicity to pericytes of advanced glycosylation end products: a possible mechanism of pericyte loss in diabetic microangiopathy. Biochem Biophys Res Commun. 1995;213:681–7.
  • Rojas A, Romay S, González D, Herrera B, Delgado R, Otero K. Regulation of endothelial nitric oxide synthase expression by albumin-derived advanced glycosylation end products. Circ Res. 2000;86:E50–4.
  • Sheikpranbabu S, Haribalaganesh R, Gurunathan S. Pigment epithelium-derived factor inhibits advanced glycation end-products-induced cytotoxicity in retinal pericytes. Diabetes Metab.
  • Yamagishi S, Inagaki Y, Amano S, Okamoto T, Takeuchi M, Makita Z. Pigment epithelium-derived factor protects cultured retinal pericytes from advanced glycation end product-induced injury through its antioxidative properties. Biochem Biophys Res Commun. 2002;296:877–82.
  • Amano S, Yamagishi S, Inagaki Y, Nakamura K, Takeuchi M, Inoue H et al. Pigment epithelium- derived factor inhibits oxidative stress-induced apoptosis and dysfunction of cultured retinal pericytes. Microvasc Res. 2005;69:45–55.
  • Yamagishi SI, Nakamura K, Ueda S, Kato S, Imaizumi T. Pigment epithelium-derived factor (PEDF) blocks angiotensin II signaling in endothelial cells via suppression of NADPH oxidase: a novel anti-oxidative mechanism of PEDF. Cell Tissue Res. 2005;320:437–45.
  • Yamagishi SI, Matsui T, Nakamura K, Yoshida T, Takeuchi M, Inoue H et al. Pigment-epithelium- derived factor suppresses expression of receptor for advanced glycation end products in the eye of diabetic rats. Ophthalmic Res. 2007;39:92–7.
  • Yamagishi S, Matsui T. Advanced glycation end products (AGEs), oxidative stress and diabetic retinopathy. Curr Pharm Biotechnol. 2011;12:362–8
  • Correspondence Address / Yazışma Adresi
Toplam 49 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Bölüm Derleme
Yazarlar

Burcu İlçe Bu kişi benim

Yayımlanma Tarihi 14 Eylül 2015
Yayımlandığı Sayı Yıl 2015 Cilt: 24 Sayı: 3

Kaynak Göster

AMA İlçe B. Pigment Epithelium-Derived Factor (PEDF): A Multifaceted and Functional New Therapeutic Agent. aktd. Eylül 2015;24(3):283-295. doi:10.17827/aktd.14318