Pigment epithelium-derived factor protects cultured retinal pericytes from advanced glycation end product-induced injury through its antioxidative properties.
Pigment epithelium-derived factor (PEDF) has recently been shown to be the most potent inhibitor of angiogenesis in the mammalian eye, suggesting that loss of PEDF is involved in the pathogenesis of proliferative diabetic retinopathy. However, a protective role for PEDF in pericyte loss in early diabetic retinopathy remains to be elucidated. In this study, we investigated whether PEDF proteins could protect against advanced glycation end product (AGE)-induced injury in retinal pericytes. Ligand blot analysis revealed that pericytes possessed a membrane protein with binding affinity for PEDF. PEDF proteins were found to significantly inhibit AGE-induced reactive oxygen species (ROS) generation and the subsequent decrease in DNA synthesis and apoptotic cell death in pericytes. Further, PEDF proteins completely restored the down-regulation of bcl-2 gene expression in AGE-exposed pericytes. The results demonstrated that PEDF proteins protected cultured pericytes from AGE-induced cytotoxicity through its anti-oxidative properties. Our present study suggests that substitution of PEDF proteins may be a promising strategy in treatment of patients with early diabetic retinopathy.
Yamagishi
Sho-ichi
S
Division of Endocrinology and Metabolism, Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan. shoichi@med.kurume-u.ac.jp
Inagaki
Yosuke
Y
Amano
Shinjiro
S
Okamoto
Tamami
T
Takeuchi
Masayoshi
M
Makita
Zenji
Z
D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis; D015153:Blotting, Western; D002455:Cell Division; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival; D004247:DNA / Q000096:biosynthesis; D018076:DNA, Complementary / Q000378:metabolism; D003902:Detergents / Q000494:pharmacology; D003930:Diabetic Retinopathy; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D005136:Eye Proteins; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D009414:Nerve Growth Factors; D020286:Pericytes / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species; D012160:Retina / Q000166:cytology*; D015843:Serpins / Q000378:metabolism*; D014162:Transfection; D051028:bcl-2-Associated X Protein; D000099174:Pigment Epithelium-Derived Factor
D000975:Antioxidants; D004247:DNA; D018076:DNA, Complementary; D003902:Detergents; D005136:Eye Proteins; D017127:Glycation End Products, Advanced; D009414:Nerve Growth Factors; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D015843:Serpins; D051028:bcl-2-Associated X Protein; D000099174:Pigment Epithelium-Derived Factor