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- Title
Pigment epithelium-derived factor prevents advanced glycation end products-induced monocyte chemoattractant protein-1 production in microvascular endothelial cells by suppressing intracellular reactive oxygen species generation Y. Inagaki et al.: Role of PEDF in diabetic retinopathy
- Authors
Inagaki, Y.; Yamagishi, S.; Okamoto, T.; Takeuchi, M.; Amano, S.
- Abstract
Aims/hypothesis. Monocytes and macrophages accumulate in the lesion of the diabetic retina, which are most likely involved in the progression of diabetic retinopathy. The levels of monocyte chemoattractant protein-1 (MCP-1) in vitreous fluids were associated with the severity of proliferative diabetic retinopathy. Recently, pigment epithelium-derived factor has been shown to be involved in the pathogenesis of proliferative diabetic retinopathy. However, a role of pigment epithelium-derived factor in monocyte recruitments in diabetic retinopathy remains to be elucidated. In this study, we investigated effects of purified pigment epithelium-derived factor on AGE-induced reactive oxygen species generation, MCP-1 mRNA up-regulation and protein production in human cultured microvascular endothelial cells. Methods. The intracellular formation of reactive oxygen species was measured using the fluorescent probe CM-H2DCFDA. MCP-1 gene expression was analysed in quantitative reverse transcription-polymerase chain reaction. Monocyte chemoattractant protein-1 production by microvascular endothelial cells was measured with an ELISA system. Results. AGE increased intracellular reactive oxygen species generation in microvascular endothelial cells. Pigment epithelium-derived factor inhibited the AGE-induced reactive oxygen species generation in a dose-dependent manner. An anti-oxidant, N-acetylcysteine, or pigment epithelium-derived factor completely prevented the AGE-induced up-regulation of MCP-1 mRNA contents as well as protein production in microvascular endothelial cells. Conclusions/interpretations. Pigment epithelium-derived factor inhibits the AGE-induced reactive oxygen species generation and the subsequent increase in MCP-1 production in microvascular endothelial cells. Our study suggests that substitution of pigment epithelium-derived factor could prevent the progression of diabetic retinopathy by attenuating the deleterious effects of AGE.
- Subjects
DIABETIC retinopathy; RETINAL diseases; DIABETES complications; MONOCYTES; ENDOCRINOLOGY; INTERNAL medicine
- Publication
Diabetologia, 2003, Vol 46, Issue 2, p284
- ISSN
0012-186X
- Publication type
Article
- DOI
10.1007/s00125-002-1013-4