Receptor for advanced glycation end-products may mediate the upregulation of hypoxia-induced early growth response-1 in mouse aorta
10.3760/cma.j.issn.0254-9026.2013.04.026
- VernacularTitle:晚期糖基化终末产物受体介导急性缺氧诱导的早期生长反应因子-1表达上调
- Author:
Chun HUANG
;
Ming YANG
;
Xiaoyun SHI
;
Xiaochun CHEN
- Publication Type:Journal Article
- Keywords:
Anoxia;
Glycosylation end-products,advanced;
Early growth response protein
- From:Chinese Journal of Geriatrics
2013;(4):444-447
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the impact of hypoxia on the expression of early growth response-1 (Egr-1) and monocyte chemoattractant protein-1 (MCP-1) in mouse aorta,and to probe the underlying mechanism involving receptor for advanced glycation end-products (RAGE).Methods 3-month-old C57BL/6 mice were subjected to hypoxia [(6.0±0.5) ％ oxygen] to establish the global hypoxia model(n=6 rats for each).Aortas were dissected,Egr-1 mRNA and MCP-1 mRNA were detected by real time RT-PCR,Egr-1 and RAGE proteins were tested by Western blot,and Egr-1 DNA binding activity was assayed by electrophoretic mobility shift assay (EMSA).For blockade of RAGE,mice were pretreated with soluble RAGE (sRAGE) for 1 h by intra-peritoneal injection before they were exposed to hypoxia.Mice with normoxia were used as controls.Results After 30 minutes of hypoxic exposure,Egr-1 mRNA in aorta was increased to (28.3±0.9)folds compared with normoxic controls (F=617.17,P＜0.01),and the induction persisted for at least 3 hours.After 45 minutes of hypoxic exposure,Egr-1 proteins in aorta was increased to (5.7 ± 0.3) folds compared with normoxic controls (F =57.18,P＜ 0.01); the enhanced DNA binding activity of Egr-1 by hypoxia was attenuated by pretreatment with anti-Egr-1 lgG.After 4 hours of hypoxic exposure,MCP-1 mRNA expression in aorta was increased to(4.0±0.3)folds compared with normoxic controls (F=30.68,P＜0.01).RAGE antigen was increased significantly within 30 minutes of hypoxic exposure,with the peak at 15 minutes; hypoxia-induced Egr-1 mRNA expression was significantly attenuated by pretreatment with sRAGE (3.3 ± 0.2) folds compared with normoxic controls (F =30.20,P＜0.01).Conclusions Hypoxia significantly induces Egr-1 and MCP-1 upregulation expressions in mouse aorta,and blockade of RAGE significantly attenuates hypoxia-induced Egr-1 expression.Thcsc findings suggest RAGE signaling is involved in hypoxia-induced vascular inflammatory stress,and highlight this receptor as a potential therapeutic target to protect tissues injured by hypoxia.
