Sparvero Louis J, Asafu-Adjei Denise, Kang Rui, Tang Daolin, Amin Neilay, Im Jaehyun, Rutledge Ronnye, Lin Brenda, Amoscato Andrew A, Zeh Herbert J, Lotze Michael T
Departments of Surgery and Bioengineering, University of Pittsburgh Cancer Institute, Pittsburgh, USA.
J Transl Med. 2009 Mar 17;7:17. doi: 10.1186/1479-5876-7-17.
The Receptor for Advanced Glycation Endproducts [RAGE] is an evolutionarily recent member of the immunoglobulin super-family, encoded in the Class III region of the major histocompatability complex. RAGE is highly expressed only in the lung at readily measurable levels but increases quickly at sites of inflammation, largely on inflammatory and epithelial cells. It is found either as a membrane-bound or soluble protein that is markedly upregulated by stress in epithelial cells, thereby regulating their metabolism and enhancing their central barrier functionality. Activation and upregulation of RAGE by its ligands leads to enhanced survival. Perpetual signaling through RAGE-induced survival pathways in the setting of limited nutrients or oxygenation results in enhanced autophagy, diminished apoptosis, and (with ATP depletion) necrosis. This results in chronic inflammation and in many instances is the setting in which epithelial malignancies arise. RAGE and its isoforms sit in a pivotal role, regulating metabolism, inflammation, and epithelial survival in the setting of stress. Understanding the molecular structure and function of it and its ligands in the setting of inflammation is critically important in understanding the role of this receptor in tumor biology.
晚期糖基化终产物受体（RAGE）是免疫球蛋白超家族中进化较新的成员，由主要组织相容性复合体的III类区域编码。RAGE仅在肺中以易于测量的水平高表达，但在炎症部位迅速增加，主要存在于炎症细胞和上皮细胞上。它以膜结合蛋白或可溶性蛋白的形式存在，上皮细胞中的应激可使其明显上调，从而调节其代谢并增强其中心屏障功能。RAGE被其配体激活和上调会导致存活率提高。在营养物质或氧合受限的情况下，通过RAGE诱导的存活途径持续发出信号会导致自噬增强、细胞凋亡减少，以及（在ATP耗竭时）坏死。这会导致慢性炎症，在许多情况下也是上皮恶性肿瘤发生的环境。RAGE及其异构体起着关键作用，在应激情况下调节代谢、炎症和上皮细胞存活。了解其在炎症情况下的分子结构和功能以及其配体对于理解该受体在肿瘤生物学中的作用至关重要。
