Semin Thromb Hemost 2000; 26(5): 485-494
DOI: 10.1055/s-2000-13204
Copyright © 2000 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

RAGE: A Multiligand Receptor Contributing to the Cellular Response in Diabetic Vasculopathy and Inflammation

Ann-Marie Schmidt, Marion Hofmann, Akihiko Taguchi, Shi Du Yan, David M. Stern
  • Departments of Surgery, Physiology and Cellular Biophysics, and Pathology, College of Physicians and Surgeons of Columbia University, New York, New York
Further Information

Publication History

Publication Date:
31 December 2000 (online)

ABSTRACT

RAGE is a multiligand member of the immunoglobulin superfamily of cell surface molecules whose properties extend the paradigm of ligand-receptor interactions. The receptor recognizes families of ligands with diverse structural features, such as advanced glycation endproducts (AGEs), amyloidogenic peptides/polypeptides, amphoterins, and S100/calgranulins rather than individual species. Engagement of RAGE by its ligands upregulates the receptor and initiates a cycle of sustained cellular perturbation; increased levels of RAGE on the cell surface make it an ideal target for subsequent ligand interactions and for propagating cellular dysfunction. At this time, the only means known to break this apparently vicious cycle appears to be blocking access to RAGE or removing the ligands. Taken together, these data suggest that RAGE has the potential to function as a progression factor in a range of disorders (AGEs are relevant to diabetes and other settings of oxidant stress, amyloidogenic peptides are relevant to amyloidoses, S100/calgranulins are relevant to inflammatory disorders, etc.) in which its ligands accumulate. The chronic juxtaposition of ligand and receptor triggers sustained cellular perturbation favoring mechanisms eventuating in tissue injury rather than those that would restore homeostasis.

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