Yan Shi Fang, Ramasamy Ravichandran, Schmidt Ann Marie
Division of Surgical Science, Department of Surgery, Columbia University Medical Center, New York, NY 10032, USA.
Nat Clin Pract Endocrinol Metab. 2008 May;4(5):285-93. doi: 10.1038/ncpendmet0786. Epub 2008 Mar 11.
Many important biochemical mechanisms are activated in the presence of high levels of glucose, which occur in diabetes. Elevated levels of glucose accelerate the formation of advanced glycation end-products (AGEs). Via their chief signaling receptor-the AGE-specific receptor (commonly abbreviated as RAGE)-AGEs generate reactive oxygen species and activate inflammatory signaling cascades. Consequently, AGEs have key roles in the pathogenesis of diabetic complications. Two discoveries have advanced our knowledge of the roles of RAGE in inflammation. First, this receptor has multiple ligands and binds not only AGEs but also proinflammatory, calcium-binding S100 proteins (also known as calgranulins) and nuclear high mobility group protein box-1. Second, RAGE is expressed on T lymphocytes, monocytes and macrophages; RAGE expression on T lymphocytes is essential for effective priming of immune responses in vivo. In this Review, we chronicle roles for RAGE in the pathogenesis of diabetic complications and develop the hypothesis that, in addition to RAGE's central role in the inflammatory response, it is critically linked to the pathogenesis of types 1 and 2 diabetes.
许多重要的生化机制在高血糖水平下被激活，而高血糖水平出现在糖尿病患者体内。血糖水平升高会加速晚期糖基化终末产物（AGEs）的形成。通过其主要信号受体——AGE特异性受体（通常简称为RAGE），AGEs会产生活性氧并激活炎症信号级联反应。因此，AGEs在糖尿病并发症的发病机制中起着关键作用。两项发现推进了我们对RAGE在炎症中作用的认识。第一，该受体有多种配体，不仅能结合AGEs，还能结合促炎的、钙结合的S100蛋白（也称为钙粒蛋白）和核高迁移率族蛋白盒1。第二，RAGE在T淋巴细胞、单核细胞和巨噬细胞上表达；T淋巴细胞上的RAGE表达对于体内有效启动免疫反应至关重要。在本综述中，我们记述了RAGE在糖尿病并发症发病机制中的作用，并提出假说，即除了RAGE在炎症反应中的核心作用外，它还与1型和2型糖尿病的发病机制密切相关。
