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

William Kim, Barry 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 journalArticle

80 Citations (Scopus)

Abstract

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
Pages (from-to)553-561
Number of pages9
JournalAnnals of the New York Academy of Sciences
Volume1043
DOIs
StatePublished - Aug 22 2005
Externally publishedYes

Fingerprint

Diabetes Complications
Medical problems
Ligands
Leukocyte L1 Antigen Complex
Tissue
HMGB1 Protein
Advanced Glycosylation End Product-Specific Receptor
Journey
Complications
Diabetes
Podocytes
Inbred NOD Mouse
Lymphocytes
Sequence Deletion
Endothelial cells
Phagocytes
Microvessels
Type 1 Diabetes Mellitus
Vascular Smooth Muscle
Hyperglycemia

Keywords

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

ASJC Scopus subject areas

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

Cite this

Receptor for advanced glycation end products and its ligands : A journey from the complications of diabetes to its pathogenesis. / Kim, William; Hudson, Barry; Moser, Bernhard; Guo, Jiancheng; Rong, Ling Ling; Lu, Yan; Qu, Wu; Lalla, Evanthia; Lerner, Shulamit; Chen, Yali; Yan, Shirley Shi Du; D'Agati, Vivette; Naka, Yoshifumi; Ramasamy, Ravichandran; Herold, Kevan; Yan, Shi Fang; Schmidt, Ann Marie.

In: Annals of the New York Academy of Sciences, Vol. 1043, 22.08.2005, p. 553-561.

Research output: Contribution to journalArticle

Kim, W, Hudson, B, Moser, B, Guo, J, Rong, LL, Lu, Y, Qu, W, Lalla, E, Lerner, S, Chen, Y, Yan, SSD, D'Agati, V, Naka, Y, Ramasamy, R, Herold, K, Yan, SF & Schmidt, AM 2005, 'Receptor for advanced glycation end products and its ligands: A journey from the complications of diabetes to its pathogenesis', Annals of the New York Academy of Sciences, vol. 1043, pp. 553-561. https://doi.org/10.1196/annals.1338.063
Kim, William ; Hudson, Barry ; Moser, Bernhard ; Guo, Jiancheng ; Rong, Ling Ling ; Lu, Yan ; Qu, Wu ; Lalla, Evanthia ; Lerner, Shulamit ; Chen, Yali ; Yan, Shirley Shi Du ; D'Agati, Vivette ; Naka, Yoshifumi ; Ramasamy, Ravichandran ; Herold, Kevan ; Yan, Shi Fang ; Schmidt, Ann Marie. / Receptor for advanced glycation end products and its ligands : A journey from the complications of diabetes to its pathogenesis. In: Annals of the New York Academy of Sciences. 2005 ; Vol. 1043. pp. 553-561.
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AU - Naka, Yoshifumi

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