Cited by 99Advanced Glycation End Products researchGalectins and Cancer BiologyChronic Kidney Disease and Diabetes

Role of galectin-3 in diabetic nephropathy

Iacobini, Carla, Amadio, Lorena, Oddi, Giovanna, Ricci, Carlo, Barsotti, Paola, Missori, Serena, Sorcini, Mariella, Di Mario, Umberto +2 more·2003·Journal of the American Society of Nephrology

Abstract

The advanced glycosylation end products (AGE) participate in the pathogenesis of nephropathy and other diabetic complications through several mechanisms, including their binding to cell surface receptors. The AGE receptors include RAGE, the macrophage scavenger receptors, OST-48 (AGE-R1), 80K-H (AGE-R2), and galectin-3 (AGE-R3). Galectin-3 interacts with the beta-galactoside residues of cell surface and matrix glycoproteins via the carbohydrate recognition domain and with intracellular proteins via peptide-peptide associations mediated by its N-terminus domain. These structural properties enable galectin-3 to exert multiple functions, including the mRNA splicing activity, the control of cell cycle, the regulation of cell adhesion, the modulation of allergic reactions, and the binding of AGE. The lack of transmembrane anchor sequence or signal peptide suggests that it is associated with other AGE receptors, possibly AGE-R1 and AGE-R2, to form an AGE-receptor complex, rather than playing an independent role. In target tissues of diabetic vascular complications, such as the endothelium and mesangium, galectin-3 is weakly expressed under basal conditions and is markedly upregulated by the diabetic milieu (and to a lesser extent by aging). Galectin-3-deficient mice were found to develop accelerated diabetic glomerulopathy versus the wild-type animals, as evidenced by the more pronounced increase in proteinuria, mesangial expansion, and matrix gene expression. This was associated with a more marked renal/glomerular AGE accumulation, suggesting that it was attributable to the lack of galectin-3 AGE-receptor function. These data indicate that galectin-3 is upregulated under diabetic conditions and is operating in vivo to provide protection toward AGE-induced tissue injury, as opposed to RAGE.

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Crossref · 10.1097/01.asn.0000077402.95720.b4

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Authors
Iacobini, C., Amadio, L., Oddi, G., Ricci, C., Barsotti, P., Missori, S., Sorcini, M., Di Mario, U., Pricci, F., & Pugliese, G.
Affiliations
  • Istituto Superiore di Sanità (IT)
  • Sapienza University of Rome (IT)
Corresponding author
  • Iacobini, Carla
  • Amadio, Lorena
  • Oddi, Giovanna
  • Sorcini, Mariella
  • Pricci, Flavia
Venue
Journal of the American Society of Nephrology
Published
2003-08
Volume
14
Issue
suppl_3
Pages
S264-S270
ISSN
1046-6673 (ISSN-L)
OpenAlex
W2151401469
Cited by
99
References
49
Citations by year
2025: 2 · 2024: 2 · 2023: 5 · 2022: 4 · 2021: 3 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 5 · 2016: 8 · 2015: 8 · 2014: 8 · 2013: 2 · 2012: 7
FWCI
2.09
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of the American Society of Nephrology (publishedVersion)
  • PubMed (publishedVersion)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
  • Life Sciences › Immunology and Microbiology › Immunology › Galectins and Cancer Biology
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
Keywords
galectin-3, diabetic nephropathy, advanced glycation end products, AGE receptor, RAGE, carbohydrate recognition domain, diabetic glomerulopathy, proteinuria, mesangial expansion, extracellular matrix gene expression, endothelium, mesangium
MeSH terms
Receptor for Advanced Glycation End Products, Animals, Diabetic Nephropathies, Humans, Receptors, Immunologic, Structure-Activity Relationship, Glycation End Products, Advanced, Cytoprotection, Galectin 3

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