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

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

Research output: Contribution to journalArticle

184 Citations (Scopus)

Abstract

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
Pages (from-to)1383-1395
Number of pages13
JournalJournal of the American Society of Nephrology
Volume14
Issue number5
DOIs
StatePublished - May 1 2003
Externally publishedYes

Fingerprint

Diabetic Nephropathies
Podocytes
Leukocyte L1 Antigen Complex
Ligands
Kidney
Albuminuria
Advanced Glycosylation End Product-Specific Receptor
glucose receptor
Wounds and Injuries
Sclerosis
Hyperglycemia
Blood Vessels
Blood Glucose
Immunoglobulins
Up-Regulation

ASJC Scopus subject areas

  • Nephrology

Cite this

Glucose, glycation, and RAGE : Implications for amplification of cellular dysfunction in diabetic nephropathy. / Wendt, Thoralf; Tanji, Nozomu; Guo, Jiancheng; Hudson, Barry; Bierhaus, Angelika; Ramasamy, Ravichandran; Arnold, Bernd; Nawroth, Peter P.; Yan, Shi Fang; D'Agati, Vivette; Schmidt, Ann Marie.

In: Journal of the American Society of Nephrology, Vol. 14, No. 5, 01.05.2003, p. 1383-1395.

Research output: Contribution to journalArticle

Wendt, T, Tanji, N, Guo, J, Hudson, B, Bierhaus, A, Ramasamy, R, Arnold, B, Nawroth, PP, Yan, SF, D'Agati, V & Schmidt, AM 2003, 'Glucose, glycation, and RAGE: Implications for amplification of cellular dysfunction in diabetic nephropathy', Journal of the American Society of Nephrology, vol. 14, no. 5, pp. 1383-1395. https://doi.org/10.1097/01.ASN.0000065100.17349.CA
Wendt, Thoralf ; Tanji, Nozomu ; Guo, Jiancheng ; Hudson, Barry ; Bierhaus, Angelika ; Ramasamy, Ravichandran ; Arnold, Bernd ; Nawroth, Peter P. ; Yan, Shi Fang ; D'Agati, Vivette ; Schmidt, Ann Marie. / Glucose, glycation, and RAGE : Implications for amplification of cellular dysfunction in diabetic nephropathy. In: Journal of the American Society of Nephrology. 2003 ; Vol. 14, No. 5. pp. 1383-1395.
@article{30353fbbf5a14987ac71312f54b7ee41,
title = "Glucose, glycation, and RAGE: Implications for amplification of cellular dysfunction in diabetic nephropathy",
abstract = "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.",
author = "Thoralf Wendt and Nozomu Tanji and Jiancheng Guo and Barry Hudson and Angelika Bierhaus and Ravichandran Ramasamy and Bernd Arnold and Nawroth, {Peter P.} and Yan, {Shi Fang} and Vivette D'Agati and Schmidt, {Ann Marie}",
year = "2003",
month = "5",
day = "1",
doi = "10.1097/01.ASN.0000065100.17349.CA",
language = "English",
volume = "14",
pages = "1383--1395",
journal = "Journal of the American Society of Nephrology",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "5",

}

TY - JOUR

T1 - Glucose, glycation, and RAGE

T2 - Implications for amplification of cellular dysfunction in diabetic nephropathy

AU - Wendt, Thoralf

AU - Tanji, Nozomu

AU - Guo, Jiancheng

AU - Hudson, Barry

AU - Bierhaus, Angelika

AU - Ramasamy, Ravichandran

AU - Arnold, Bernd

AU - Nawroth, Peter P.

AU - Yan, Shi Fang

AU - D'Agati, Vivette

AU - Schmidt, Ann Marie

PY - 2003/5/1

Y1 - 2003/5/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0037406905&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037406905&partnerID=8YFLogxK

U2 - 10.1097/01.ASN.0000065100.17349.CA

DO - 10.1097/01.ASN.0000065100.17349.CA

M3 - Article

C2 - 12707408

AN - SCOPUS:0037406905

VL - 14

SP - 1383

EP - 1395

JO - Journal of the American Society of Nephrology

JF - Journal of the American Society of Nephrology

SN - 1046-6673

IS - 5

ER -