Up-regulation of vascular endothelial growth factor and down-regulation of pigment epithelium-derived factor messenger ribonucleic acid levels in leptin-exposed cultured retinal pericytes.
Leptin, a circulating hormone secreted mainly from adipose tissues, is involved in the control of body weight. Recently, leptin was found to be an angiogenic factor and its vitreous levels were shown to be elevated in patients with angiogenic eye diseases such as proliferative diabetic retinopathy. However, the role of leptin in diabetic retinopathy is not fully understood. Since pericyte loss and dysfunction have been considered to be one of the characteristic changes of the early phases of diabetic retinopathy, we investigated the effects of leptin on the growth and function of bovine cultured retinal pericytes. Although it did not affect cell growth, leptin significantly up-regulated pericyte messenger ribonucleic acid levels of an endogenous angiogenic stimulator, vascular endothelial growth factor (VEGF). Leptin was also found to significantly inhibit gene expression of pigment epithelium-derived factor (PEDF), the most potent angiogenesis inhibitor in the mammalian eye, in pericytes. The present study suggests that leptin might elicit angiogenesis through VEGF induction as well as PEDF suppression in pericytes and could thus be involved in the development and progression of diabetic retinopathy, especially in obese insulin-resistant patients.
Yamagishi
S
S
Division of Endocrinology and Metabolism, Department of Medicine, Kurume University School of Medicine, Kurume, Japan. shoichi@med.kurume-u.ac.jp
Inagaki
Y
Y
Amano
S
S
Okamoto
T
T
Takeuchi
M
M
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D015536:Down-Regulation; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*; D005136:Eye Proteins; D005786:Gene Expression Regulation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D020738:Leptin / Q000494:pharmacology* / Q000502:physiology; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism*; D009414:Nerve Growth Factors; D020286:Pericytes / Q000187:drug effects / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012171:Retinal Vessels / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000099174:Pigment Epithelium-Derived Factor
D004247:DNA; D016228:Endothelial Growth Factors; D005136:Eye Proteins; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D008222:Lymphokines; D009414:Nerve Growth Factors; D011506:Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015843:Serpins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000099174:Pigment Epithelium-Derived Factor