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RAGE及其剪接变体与糖尿病血管并发症
作者:任晓妹 孙子林 
单位:东南大学附属中大医院,内分泌科,江苏,南京,210009
关键词:糖基化终产物 糖基化终产物受体 剪接变体 内源分泌型糖基化终产物受体 糖尿病血管病变 
分类号:R587.2
出版年·卷·期(页码):2005·24·第二期(138-141)
摘要:

糖尿病血管病变是一种多因素疾病.糖基化终产物(AGE)与其受体(RAGE)相互作用在糖尿病血管病变的发展中起重要作用.RAGE转基因的糖尿病小鼠其肾脏病变更严重,应用AGE阻滞剂可阻断并发症的发生.目前已经发现了可诱导RAGE基因表达的细胞外信号及核因子,这些因素也被认为是糖尿病并发症的危险因素.通过分析RAGE多聚核糖体mRNA发现了3种主要的剪接变体:截去C端型、截去N端型和已知的全长型.人们把前者即可溶型RAGE命名为内源分泌型RAGE(esRAGE),esRAGE可捕获AGE配体,中和AGE对内皮细胞的损伤活性,提示其有潜在的保护糖尿病性血管损伤的作用.

Diabetic vasculopathy is a multifactor disease. AGE-RAGE interactions are thought to play a central role in the development of diabetic vascular complications.When made as a diabetic model,RAGE-overexpressing transgenic mice exhibited the exacerbation of the indices of nephropathy, and this was prevented by the inhibition of AGE formation. Extracellular signals and nuclear factors that induce the transcription of human RAGE gene were identified, which could be regard as risk factors of diabetic complications. Through an analysis of polysomal mRNAs for RAGE, three major variants were isolated:novel C-terminally and N-terminally truncated forms and the known full-length form. The former, soluble form of RAGE,named endogenous secretory RAGE(esRAGE), was able to capture AGE ligands and neutralize the AGE action on endothelial cells, suggesting that this variant has a potential to protect blood vessels from diabetes-induced injury.

参考文献:

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