Glucose, glycation, and RAGE: Implications for amplification of cellular dysfunction in diabetic nephropathy

Thoralf Wendt, Nozomu Tanji, Jiancheng Guo, Barry I. Hudson, Angelika Bierhaus, Ravichandran Ramasamy, Bernd Arnold, Peter P. Nawroth, Shi Fang Yan, Vivette D'Agati, Ann Marie Schmidt

Research output: Contribution to journalArticlepeer-review

205 Scopus citations


Receptor for advanced glycation endproducts (RAGE) is a multi-ligand member of the immunoglobulin superfamily of cell surface molecules. Driven by rapid accumulation and expression of key ligands such as advanced glycation endproducts (AGE) and S100/calgranulins in diabetic tissues, upregulation and activation of RAGE magnifies cellular perturbation in tissues affected by hyperglycemia, such as the large blood vessels and the kidney. In the diabetic glomerulus, RAGE is expressed principally by glomerular visceral epithelial cells (podocytes). Blockade of RAGE in the hyperglycemic db/db mouse suppresses functional and structural alterations in the kidney, in the absence of alterations in blood glucose. Recent studies in homozygous RAGE null mice support a key role for RAGE in glomerular perturbation in diabetes. Importantly, beyond diabetes, studies in other settings of glomerulopathies support a critical RAGE-dependent pathway in podocytes linked to albuminuria, mesangial expansion, and glomerular sclerosis. A new paradigm is propsed in glomerular injury, and it is suggested that blockade of the RAGE axis may provide a novel means to prevent irreparable glomerular injury in diabetes and other sclerosing glomerulopathies.

Original languageEnglish (US)
Pages (from-to)1383-1395
Number of pages13
JournalJournal of the American Society of Nephrology
Issue number5
StatePublished - May 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology


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