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- AGE-RAGE signaling pathway in diabetic complications
description
Advanced glycation end products (AGEs) are a complex group of compounds produced through the non-enzymatic glycation and oxidation of proteins, lipids and nucleic acids, primarily due to aging and under certain pathologic condition such as huperglycemia. Some of the best chemically characterized AGEs include N-epsilon-carboxy-methyl-lysine (CML), N-epsilon-carboxy-ethyl-lysine (CEL), and Imidazolone. The major receptor for AGEs, known as receptor for advanced glycation end products (RAGE or AGER), belongs to the immunoglobulin superfamily and has been described as a pattern recognition receptor. AGE/RAGE signaling elicits activation of multiple intracellular signal pathways involving NADPH oxidase, protein kinase C, and MAPKs, then resulting in NF-kappaB activity. NF-kappa B promotes the expression of pro-inflammatory cytokines such as IL-1, IL-6 and TNF-alpha and a variety of atherosclerosis-related genes, including VCAM-1, tissue factor, VEGF, and RAGE. In addition, JAK-STAT-mediated and PI3K-Akt-dependent pathways are induced via RAGE, which in turn participate in cell proliferation and apoptosis respectively. Hypoxia-mediated induction of Egr-1 was also shown to require the AGE-RAGE interaction. The results of these signal transductions have been reported to be the possible mechanism that initates diabetic complications
external resources
NCBI:1319988
KEGG:hsa04933
PUBMED:23776698
PUBMED:15569303
PUBMED:16894049
PUBMED:18323529
PUBMED:11375353
PUBMED:21111800
PUBMED:19404313
PUBMED:20470857
PUBMED:17005604
PUBMED:23961320
PUBMED:21261520
PUBMED:11180401
PUBMED:18922799
PUBMED:21680901
PUBMED:11684565
PUBMED:21590515
PUBMED:12709399
PUBMED:20300563
PUBMED:21440603
PUBMED:22558488
genes
AGER
,
AGTR1
,
AKT1
,
AKT2
,
BAX
,
CCND1
,
BCL2
,
CASP3
,
CDC42
,
CDK4
,
CDKN1B
,
COL1A1
,
COL1A2
,
COL3A1
,
COL4A1
,
COL4A2
,
COL4A3
,
COL4A4
,
COL4A5
,
COL4A6
,
MAPK14
,
CYBB
,
DIAPH1
,
EDN1
,
EGR1
,
F3
,
VEGFD
,
FOXO1
,
FN1
,
HRAS
,
ICAM1
,
IL1A
,
IL1B
,
IL6
,
CXCL8
,
JAK2
,
JUN
,
KRAS
,
SMAD2
,
SMAD3
,
SMAD4
,
MMP2
,
NFATC1
,
NFKB1
,
NOS3
,
NRAS
,
SERPINE1
,
PIK3CA
,
PIK3CB
,
PIM1
,
PIK3CD
,
PIK3R1
,
PIK3R2
,
PLCB2
,
PLCB3
,
PLCB4
,
PLCD1
,
PLCG1
,
PLCG2
,
PRKCA
,
PRKCB
,
PRKCD
,
PRKCE
,
PRKCZ
,
MAPK1
,
MAPK3
,
MAPK8
,
MAPK11
,
MAPK9
,
MAPK10
,
MAPK13
,
RAC1
,
RELA
,
MAPK12
,
CCL2
,
SELE
,
STAT1
,
STAT3
,
STAT5A
,
STAT5B
,
TGFB1
,
TGFB2
,
TGFB3
,
TGFBR1
,
TGFBR2
,
THBD
,
TNF
,
VCAM1
,
VEGFA
,
VEGFB
,
VEGFC
,
PIK3R3
,
AKT3
,
PLCB1
,
NOX1
,
NOX3
,
PLCE1
,
PLCD4
,
PLCD3
,