Role of Advanced Glycation End Products in Diabetic Nephropathy
Abstract
Nonenzymatic reactions between sugars and the free amino groups on proteins, lipids, and nucleic acids result in molecular dysfunction through the formation of advanced glycation end products (AGE). AGE have a wide range of chemical, cellular, and tissue effects through changes in charge, solubility, and conformation that characterize molecular senescence. AGE also interact with specific receptors and binding proteins to influence the expression of growth factors and cytokines, including TGF-beta1 and CTGF, thereby regulating the growth and proliferation of the various renal cell types. It seems that many of the pathogenic changes that occur in diabetic nephropathy may be induced by AGE. Drugs that either inhibit the formation of AGE or break AGE-induced cross-links have been shown to be renoprotective in experimental models of diabetic nephropathy. AGE are able to stimulate directly the production of extracellular matrix and inhibit its degradation. AGE modification of matrix proteins is also able to disrupt matrix-matrix and matrix-cell interactions, contributing to their profibrotic action. In addition, AGE significantly interact with the renin-angiotensin system. Recent studies have suggested that angiotensin-converting enzyme inhibitors are able to reduce the accumulation of AGE in diabetes, possibly via the inhibition of oxidative stress. This interaction may be a particularly important pathway for the development of AGE-induced damage, as it also can be attenuated by antioxidant therapy. In addition to being a consequence of oxidative stress, it is now clear that AGE can promote the generation of reactive oxygen species. It is likely that therapies that inhibit the formation of AGE will form an important part of future therapy in patients with diabetes, acting synergistically with conventional approaches to prevent diabetic renal injury.
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AGEs are long-lived irreversibly formed molecules found in the circulatory system and tissues, particularly those with long-lasting proteins.
“AGEs are long-lived irreversibly formed molecules found in the circulatory system and tissues, particularly those with long-lasting proteins such as lens crystallins, cartilage, glomerular basement membrane, and extracellular matrix29,30.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [30]
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- Authors
- Forbes, J. M., Cooper, M. E., Oldfield, M. D., & Thomas, M. C.
- Corresponding author
- Thomas, Merlin C.
- Venue
- Journal of the American Society of Nephrology
- Published
- 2003-08
- Volume
- 14
- Issue
- suppl_3
- Pages
- S254-S258
- ISSN
- 1046-6673 (ISSN-L)
- OpenAlex
- W2096438273
- Cited by
- 351
- References
- 42
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 15 · 2023: 10 · 2022: 12 · 2021: 13 · 2020: 15 · 2019: 16 · 2018: 17 · 2017: 13 · 2016: 19 · 2015: 24 · 2014: 24 · 2013: 13 · 2012: 13
- FWCI
- 10.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the American Society of Nephrology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Keywords
- advanced glycation end products, diabetic nephropathy, AGE receptor, TGF-β1, connective tissue growth factor, renal fibrosis, extracellular matrix, renin-angiotensin system, ACE inhibitors, oxidative stress, reactive oxygen species, renal protection, AGE inhibitors, antioxidant therapy
- MeSH terms
- Animals, Diabetic Nephropathies, Growth Substances, Humans, Renin-Angiotensin System, Transcription Factors, Extracellular Matrix Proteins, Glycation End Products, Advanced
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