Gene interactions and pathways from curated databases and text-mining
J Biol Chem 2001, PMID: 11571295

Regulation of vascular endothelial growth factor expression by advanced glycation end products.

Treins, C; Giorgetti-Peraldi, S; Murdaca, J; Van Obberghen, E

Advanced glycation end products (AGEs) are generated during long term diabetes and are correlated with the development of diabetic complications, such as retinopathy. Diabetic retinopathy is characterized by an increased retinal neovascularization due to the action of the angiogenic factor, vascular endothelial growth factor (VEGF). In this report, we show that injection of insulin and glycated albumin (Alb-AGE) to mice increases VEGF mRNA expression in eyes. Insulin and Alb-AGE stimulate VEGF mRNA and protein expression in retinal epithelial cells (ARPE-19). Alb-AGE-induced VEGF expression is not modulated by the use of antioxidants, N-acetyl-l-cysteine or pyrrolidinedithiocarbamate, or by an inhibitor of phosphatidylinositol 3-kinase (PI3K), wortmannin. However, using an inhibitor of ERK activation, U0126, we show that Alb-AGE stimulates VEGF expression through an ERK-dependent pathway. Accordingly, we found that Alb-AGE activated mitogen-activate protein kinase, ERK1/2, JNK1/2, but not p38, and that Alb-AGE did not activate PI3K and PKB. Moreover, Alb-AGE activated the transcription factor, hypoxia inducible factor-1 (HIF-1) DNA binding activity. This activation is mediated by an increase in accumulation of the HIF-1alpha protein through an ERK-dependent pathway. Thus, stimulation of VEGF expression by Alb-AGE, through the activation of HIF-1, could play an important role in the development of diabetic retinopathy.

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Text Mining Data

VEGF → Alb-AGE: " Alb-AGE induced VEGF expression is not modulated by the use of antioxidants, N-acetyl-l-cysteine or pyrrolidinedithiocarbamate, or by an inhibitor of phosphatidylinositol 3-kinase (PI3K), wortmannin "

VEGF → Alb-AGE: " Alb-AGE induced VEGF expression is not modulated by the use of antioxidants, N-acetyl-l-cysteine or pyrrolidinedithiocarbamate, or by an inhibitor of phosphatidylinositol 3-kinase (PI3K), wortmannin "

VEGF → Alb-AGE: " However, using an inhibitor of ERK activation, U0126, we show that Alb-AGE stimulates VEGF expression through an ERK dependent pathway "

VEGF → Alb-AGE: " However, using an inhibitor of ERK activation, U0126, we show that Alb-AGE stimulates VEGF expression through an ERK dependent pathway "

p38 → Alb-AGE: " Accordingly, we found that Alb-AGE activated mitogen-activate protein kinase, ERK1/2, JNK1/2, but not p38 , and that Alb-AGE did not activate PI3K and PKB "

p38 → Alb-AGE: " Accordingly, we found that Alb-AGE activated mitogen-activate protein kinase, ERK1/2, JNK1/2, but not p38 , and that Alb-AGE did not activate PI3K and PKB "

ERK1/2 → Alb-AGE: " Accordingly, we found that Alb-AGE activated mitogen-activate protein kinase, ERK1/2 , JNK1/2, but not p38, and that Alb-AGE did not activate PI3K and PKB "

ERK1/2 → Alb-AGE: " Accordingly, we found that Alb-AGE activated mitogen-activate protein kinase, ERK1/2 , JNK1/2, but not p38, and that Alb-AGE did not activate PI3K and PKB "

ERK1/2 → Alb-AGE: " Accordingly, we found that Alb-AGE activated mitogen-activate protein kinase, ERK1/2 , JNK1/2, but not p38, and that Alb-AGE did not activate PI3K and PKB "

ERK1/2 → Alb-AGE: " Accordingly, we found that Alb-AGE activated mitogen-activate protein kinase, ERK1/2 , JNK1/2, but not p38, and that Alb-AGE did not activate PI3K and PKB "

transcription factor → Alb-AGE: " Moreover, Alb-AGE activated the transcription factor , hypoxia inducible factor-1 (HIF-1) DNA binding activity "

transcription factor → Alb-AGE: " Moreover, Alb-AGE activated the transcription factor , hypoxia inducible factor-1 (HIF-1) DNA binding activity "

Manually curated Databases

No curated data.