Receptor for advanced glycation end products and its ligands: A journey from the complications of diabetes to its pathogenesis

William Kim, Barry I. Hudson, Bernhard Moser, Jiancheng Guo, Ling Ling Rong, Yan Lu, Wu Qu, Evanthia Lalla, Shulamit Lerner, Yali Chen, Shirley Shi Du Yan, Vivette D'Agati, Yoshifumi Naka, Ravichandran Ramasamy, Kevan Herold, Shi Fang Yan, Ann Marie Schmidt

Research output: Contribution to journalArticlepeer-review

83 Scopus citations


Many studies have suggested that the expression of RAGE (receptor for advanced glycation end products) is upregulated in human tissues susceptible to the long-term complications of diabetes. From the kidneys to the macrovessels of the aorta, RAGE expression is upregulated in a diverse array of cell types, from glomerular epithelial cells (podocytes) to endothelial cells, vascular smooth muscle cells, and inflammatory mononuclear phagocytes and lymphocytes. Although RAGE was first described as a receptor for advanced glycation end products (AGEs), the key finding that RAGE was also a signaling receptor for proinflammatory S100/calgranulins and amphoterin, led to the premise that even in euglycemia, ligand-RAGE interaction propagated inflammatory mechanisms linked to chronic cellular perturbation and tissue injury. Indeed, such considerations suggested that RAGE might even participate in the pathogenesis of type 1 diabetes. Our studies have shown that pharmacological and/or genetic deletion/mutation of the receptor attenuates the development of hyperglycemia in NOD mice; in mice with myriad complications of diabetes, interruption of ligand-RAGE interaction prevents or delays the chronic complications of the disease in both macro- and microvessel structures. Taken together, these findings suggest that RAGE is "at the right place and time" to contribute to the pathogenesis of diabetes and it complications. Studies are in progress to test the premise that antagonism of this interaction is a logical strategy for the prevention and treatment of diabetes.

Original languageEnglish (US)
Pages (from-to)553-561
Number of pages9
JournalAnnals of the New York Academy of Sciences
StatePublished - 2005
Externally publishedYes


  • AGE
  • Atherosclerosis
  • Diabetes
  • Inflammation
  • RAGE
  • Vascular injury

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science


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