PEDF and Its Roles in Physiological and Pathological Conditions: Implication in Diabetic and Hypoxia-induced Angiogenic Diseases

Overview

Journal Clin Sci (Lond)

Specialties Biochemistry
General Medicine
Science

Date 2015 Apr 18

PMID 25881671

Citations 73

Authors

Xuemin He

Rui Cheng

Siribhinya Benyajati

Jian-Xing Ma

Affiliations

Soon will be listed here.

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.

Citing Articles

Functional Roles of Pigment Epithelium-Derived Factor in Retinal Degenerative and Vascular Disorders: A Scoping Review.

Jakobsen T, Adsersen R, Askou A, Corydon T Invest Ophthalmol Vis Sci. 2024; 65(14):41.

PMID: 39728690 PMC: 11684118. DOI: 10.1167/iovs.65.14.41.

Autophagy-dependent ferroptosis may play a critical role in early stages of diabetic retinopathy.

Sun W, An X, Zhang Y, Tang S, Sun Y, Kang X World J Diabetes. 2024; 15(11):2189-2202.

PMID: 39582563 PMC: 11580571. DOI: 10.4239/wjd.v15.i11.2189.

Pigment Epithelial-Derived Factor in Pancreatic and Liver Cancers-From Inflammation to Cancer.

Paczek S, Zajkowska M, Mroczko B Biomedicines. 2024; 12(10).

PMID: 39457573 PMC: 11504982. DOI: 10.3390/biomedicines12102260.

Reduction of pathological retinal neovascularization, vessel obliteration, and artery tortuosity by PEDF protein in an oxygen-induced ischemic retinopathy rat model.

Zhao S, Tschulakow A, Karthikeyan S, Wang K, Kochanek S, Schraermeyer U FASEB Bioadv. 2024; 6(9):311-326.

PMID: 39399476 PMC: 11467744. DOI: 10.1096/fba.2024-00059.

Crosstalk between MIR-96 and IRS/PI3K/AKT/VEGF cascade in hRPE cells; A potential target for preventing diabetic retinopathy.

Hosseinpoor Z, Soheili Z, Davari M, Latifi-Navid H, Samiee S, Samiee D PLoS One. 2024; 19(9):e0310999.

PMID: 39348384 PMC: 11441665. DOI: 10.1371/journal.pone.0310999.

References

Wang S, Gottlieb J, Sorenson C, Sheibani N . Modulation of thrombospondin 1 and pigment epithelium-derived factor levels in vitreous fluid of patients with diabetes. Arch Ophthalmol. 2009; 127(4):507-13. PMC: 2819322. DOI: 10.1001/archophthalmol.2009.53. View

Huber M, Wachtlin J . Vitreous levels of proteins implicated in angiogenesis are modulated in patients with retinal or choroidal neovascularization. Ophthalmologica. 2012; 228(3):188-93. DOI: 10.1159/000339952. View

Wang H, Feng L, Hu J, Xie C, Wang F . Characterisation of the vitreous proteome in proliferative diabetic retinopathy. Proteome Sci. 2012; 10(1):15. PMC: 3310785. DOI: 10.1186/1477-5956-10-15. View

Lee K, Hu Y, Ding L, Chen Y, Takahashi Y, Mott R . Therapeutic potential of a monoclonal antibody blocking the Wnt pathway in diabetic retinopathy. Diabetes. 2012; 61(11):2948-57. PMC: 3478529. DOI: 10.2337/db11-0300. View

Zhang L, Chen J, Ke Y, Mansel R, Jiang W . Expression of pigment epithelial derived factor is reduced in non-small cell lung cancer and is linked to clinical outcome. Int J Mol Med. 2006; 17(5):937-44. View

Cheng X, Kuzuya M, Kim W, Song H, Hu L, Inoue A . Exercise training stimulates ischemia-induced neovascularization via phosphatidylinositol 3-kinase/Akt-dependent hypoxia-induced factor-1 alpha reactivation in mice of advanced age. Circulation. 2010; 122(7):707-16. PMC: 3071504. DOI: 10.1161/CIRCULATIONAHA.109.909218. View

Zaichuk T, Shroff E, Emmanuel R, Filleur S, Nelius T, Volpert O . Nuclear factor of activated T cells balances angiogenesis activation and inhibition. J Exp Med. 2004; 199(11):1513-22. PMC: 2211785. DOI: 10.1084/jem.20040474. View

Nyengaard J, Rasch R . The impact of experimental diabetes mellitus in rats on glomerular capillary number and sizes. Diabetologia. 1993; 36(3):189-94. DOI: 10.1007/BF00399948. View

Zhang Z, Neiva K, Lingen M, Ellis L, Nor J . VEGF-dependent tumor angiogenesis requires inverse and reciprocal regulation of VEGFR1 and VEGFR2. Cell Death Differ. 2009; 17(3):499-512. PMC: 2822115. DOI: 10.1038/cdd.2009.152. View

10.

Enge M, Bjarnegard M, Gerhardt H, Gustafsson E, Kalen M, Asker N . Endothelium-specific platelet-derived growth factor-B ablation mimics diabetic retinopathy. EMBO J. 2002; 21(16):4307-16. PMC: 126162. DOI: 10.1093/emboj/cdf418. View

11.

Liu Y, Leo L, McGregor C, Grivitishvili A, Barnstable C, Tombran-Tink J . Pigment epithelium-derived factor (PEDF) peptide eye drops reduce inflammation, cell death and vascular leakage in diabetic retinopathy in Ins2(Akita) mice. Mol Med. 2012; 18:1387-401. PMC: 3533643. DOI: 10.2119/molmed.2012.00008. View

12.

Rapp M, Woo G, Al-Ubaidi M, Becerra S, Subramanian P . Pigment epithelium-derived factor protects cone photoreceptor-derived 661W cells from light damage through Akt activation. Adv Exp Med Biol. 2014; 801:813-20. PMC: 11343582. DOI: 10.1007/978-1-4614-3209-8_102. View

13.

Bai Y, Huang L, Xu X, Du W, Zhou A, Yu W . Polyethylene glycol-modified pigment epithelial-derived factor: new prospects for treatment of retinal neovascularization. J Pharmacol Exp Ther. 2012; 342(1):131-9. DOI: 10.1124/jpet.112.192575. View

14.

Matsuyama K, Ogata N, Matsuoka M, Shima C, Wada M, Jo N . Relationship between pigment epithelium-derived factor (PEDF) and renal function in patients with diabetic retinopathy. Mol Vis. 2008; 14:992-6. PMC: 2405814. View

15.

Liao H, Hyman M, Lawrence D, Pinsky D . Molecular regulation of the PAI-1 gene by hypoxia: contributions of Egr-1, HIF-1alpha, and C/EBPalpha. FASEB J. 2007; 21(3):935-49. DOI: 10.1096/fj.06-6285com. View

16.

Manalo K, Choong P, Becerra S, Dass C . Pigment epithelium-derived factor as an anticancer drug and new treatment methods following the discovery of its receptors: a patent perspective. Expert Opin Ther Pat. 2011; 21(2):121-30. PMC: 4026095. DOI: 10.1517/13543776.2011.545347. View

17.

Guan M, Yam H, Su B, Chan K, Pang C, Liu W . Loss of pigment epithelium derived factor expression in glioma progression. J Clin Pathol. 2003; 56(4):277-82. PMC: 1769929. DOI: 10.1136/jcp.56.4.277. View

18.

Cai J, Jiang W, Grant M, Boulton M . Withdrawal: Pigment epithelium-derived factor inhibits angiogenesis via regulated intracellular proteolysis of vascular endothelial growth factor receptor 1. J Biol Chem. 2005; 281(6):3604-13. DOI: 10.1074/jbc.M507401200. View

19.

Matsui T, Nishino Y, Maeda S, Yamagishi S . PEDF-derived peptide inhibits corneal angiogenesis by suppressing VEGF expression. Microvasc Res. 2012; 84(1):105-8. DOI: 10.1016/j.mvr.2012.02.006. View

20.

Yamagishi S, Nakamura K, Takenaka K, Matsui T, Jinnouchi Y, Imaizumi T . Pigment epithelium-derived factor (PEDF) promotes growth of pericytes through autocrine production of platelet-derived growth factor-B. Microvasc Res. 2005; 69(3):128-34. DOI: 10.1016/j.mvr.2005.04.001. View